{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:03:47Z","timestamp":1793721827725,"version":"4.6.1"},"reference-count":214,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Primary Sj\u00f6gren\u2019s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and inflammation. Patients often have dry mouth and dry eye symptoms, which seriously affect their lives. Improving dry mouth and eye symptoms has become a common demand from patients. For this reason, researchers have conducted many studies on external secretory glands. In this paper, we summarize recent studies on the salivary glands of pSS patients from the perspective of the immune microenvironment. These studies showed that hypoxia, senescence, and chronic inflammation are the essential characteristics of the salivary gland immune microenvironment. In the SG of pSS, genes related to lymphocyte chemotaxis, antigen presentation, and lymphocyte activation are upregulated. Interferon (IFN)-related genes,\u00a0DNA methylation, sRNA downregulation, and mitochondrial-related differentially expressed genes are also involved in forming the immune microenvironment of pSS, while multiple signaling pathways are involved in regulation. We further elucidated the regulation of the salivary gland immune microenvironment in pSS and relevant, targeted treatments.<\/jats:p>","DOI":"10.3389\/fimmu.2022.967304","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T11:44:37Z","timestamp":1663069477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Composition and regulation of the immune microenvironment of salivary gland in Sj\u00f6gren\u2019s syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhen","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205375","article-title":"Epidemiology of primary sj\u00f6gren's syndrome: A systematic review and meta-analysis","volume":"74","author":"Qin","year":"2015","journal-title":"Ann Rheumatol Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1080\/03009740310004676","article-title":"Estimating the prevalence among Caucasian women of primary sj\u00f6gren's syndrome in two general practices in Birmingham, U.K. scand","volume":"33","author":"Bowman","year":"2004","journal-title":"J Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jtos.2014.02.002","article-title":"Rethinking dry eye disease: A perspective on clinical implications","volume":"12","author":"Bron","year":"2014","journal-title":"Ocul. Surf"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1834-7819.2011.01347.x","article-title":"Risk factors and symptoms associated with xerostomia: A cross-sectional study","volume":"56","author":"Villa","year":"2011","journal-title":"Aust Dent J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2017.78.8.438","article-title":"Sj\u00f6gren's syndrome","volume":"78","author":"Thorne","year":"2017","journal-title":"Br J Hosp. Med (Lond)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket349","article-title":"Systemic involvement in primary sj\u00f6gren\u2019s syndrome evaluated by the EULAR-SS disease activity index: Analysis of 921 Spanish patients (GEAS-SS registry)","volume":"53","author":"Ramos-Casals","year":"2014","journal-title":"Rheumatol (Oxford)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0011-2016","article-title":"Pulmonary manifestations of sj\u00f6gren\u2019s syndrome","volume":"25","author":"Flament","year":"2016","journal-title":"Eur Respir Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jaut.2012.01.003","article-title":"Peripheral neuropathies in sj\u00f6gren\u2019s syndrome: A critical update on clinical features and pathogenetic mechanisms","volume":"39","author":"Pavlakis","year":"2012","journal-title":"J Autoimmun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S47399","article-title":"The epidemiology of sj\u00f6gren\u2019s syndrome","volume":"6","author":"Patel","year":"2014","journal-title":"Clin Epidemiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.144","article-title":"Epigenetics: DNA methylation signatures in sjogren syndrome","volume":"12","author":"Renaudineau","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5845849","article-title":"HIF1A (rs11549465) and AKNA (rs10817595) gene polymorphisms are associated with primary sj\u00f6gren's syndrome","volume":"2017","author":"Hern\u00e1ndez-Molina","year":"2017","journal-title":"BioMed Res Int"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216588","article-title":"Salivary gland epithelial cells from patients with sj\u00f6gren's syndrome induce b-lymphocyte survival and activation","volume":"79","author":"Rivi\u00e8re","year":"2020","journal-title":"Ann Rheum. Dis"},{"key":"B13","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jaut.2015.07.002","article-title":"Type I and II interferon signatures in sjogren's syndrome pathogenesis: Contributions in distinct clinical phenotypes and sjogren's related lymphomagenesis","volume":"63","author":"Nezos","year":"2015","journal-title":"J Autoimmun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.14219\/jada.archive.1994.0059","article-title":"Salivary gland dysfunction: Causes, symptoms, treatment","volume":"125","author":"Atkinson","year":"1994","journal-title":"J Am Dent Assoc"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.03.012","article-title":"Fcrl4+ b-cells in salivary glands of primary sj\u00f6gren\u2019s syndrome patients","volume":"81","author":"Haacke","year":"2017","journal-title":"J Autoimmun"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810169106","article-title":"Donor toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation","volume":"106","author":"Kr\u00fcger","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.14.4.633","article-title":"Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: Role of bcl-2, bcl-xL and bax in tubular injury","volume":"14","author":"Yamamoto","year":"2004","journal-title":"Int J Mol Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(98)00002-1","article-title":"Hypoxia inhibits cyclic nucleotide-stimulated epithelial ion transport: Role for nucleotide cyclases as oxygen sensors","volume":"284","author":"Taylor","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa695","article-title":"Increased expression of interleukin-21-inducible genes in minor salivary glands are associated with primary sj\u00f6gren's syndrome disease characteristics","volume":"60","author":"Xiaomin","year":"2021","journal-title":"Rheumatol (Oxford)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.008","article-title":"HIF transcription factors, inflammation, and immunity","volume":"41","author":"Palazon","year":"2014","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.07.033","article-title":"Control of TH17\/Treg balance by hypoxia-inducible factor 1","volume":"146","author":"Dang","year":"2011","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.4.2898","article-title":"Identification of IL-18 and Th17 cells in salivary glands of patients with sj\u00f6gren's syndrome, and amplification of IL-17- mediated secretion of inflammatory cytokines from salivary gland cells by IL-18","volume":"181","author":"Sakai","year":"2008","journal-title":"J Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13351","article-title":"The HIF-1\u03b1 pathway plays a critical role in salivary gland development in ex vivo organ cultures","volume":"12","author":"Tomomasa","year":"2022","journal-title":"FEBS Open Bio"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/5845849","article-title":"HIF1A (rs11549465) and AKNA (rs10817595) gene polymorphisms are associated with primary sj\u00f6gren\u2019s syndrome","volume":"2017","author":"Hern\u00e1ndez-Molina","year":"2017","journal-title":"BioMed Res Int"},{"key":"B25","doi-asserted-by":"publisher","first-page":"6794508","DOI":"10.1155\/2018\/6794508","article-title":"The process of acclimation to chronic hypoxia leads to submandibular gland and periodontal alterations: An insight on the role of inflammatory mediators","volume":"2018","author":"Terrizzi","year":"2018","journal-title":"Mediators Inflammation"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2009.10.004","article-title":"Characteristics of the minor salivary gland infiltrates in sj\u00f6gren's syndrome","volume":"34","author":"Christodoulou","year":"2010","journal-title":"J Autoimmun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201216","article-title":"Inducible tertiary lymphoid structures, autoimmunity, and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL\/6 mice","volume":"189","author":"Bombardieri","year":"2012","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1006\/clim.2002.5228","article-title":"Role of salivary IgA in the pathogenesis of sj\u00f6gren syndrome","volume":"104","author":"Berra","year":"2002","journal-title":"Clin Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2012.09.013","article-title":"Novel autoantibodies in sj\u00f6gren's syndrome","volume":"145","author":"Shen","year":"2012","journal-title":"Clin Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/j.1365-2249.2012.04606.x","article-title":"Selective localization of T helper subsets in labial salivary glands from primary sj\u00f6gren's syndrome patients","volume":"169","author":"Maehara","year":"2012","journal-title":"Clin Exp Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080246","article-title":"Foxp3+ T-regulatory cells in sj\u00f6gren's syndrome: Correlation with the grade of the autoimmune lesion and certain adverse prognostic factors","volume":"173","author":"Christodoulou","year":"2008","journal-title":"Am J Pathol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s007840100104","article-title":"Cytokine concentrations in stimulated whole saliva among patients with primary sj\u00f6gren's syndrome, secondary sj\u00f6gren's syndrome, and patients with primary sj\u00f6gren's syndrome receiving varying doses of interferon for symptomatic treatment of the condition: A preliminary study","volume":"5","author":"Streckfus","year":"2001","journal-title":"Clin Oral Investig"},{"key":"B33","article-title":"Salivary cytokine profifiles in primary sj\u00f6gren's syndrome differ from those in non-sj\u00f6gren sicca in terms of TNF-alpha levels and Th-1\/Th-2 ratios","volume":"29","author":"Kang","year":"2011","journal-title":"Clin Exp Rheumatol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4000","article-title":"Cellular senescence in aging and age-related disease: From mechanisms to therapy","volume":"21","author":"Childs","year":"2015","journal-title":"Nat Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/art.40659","article-title":"Salivary gland stem cells age prematurely in primary sj\u00f6gren's syndrome","volume":"71","author":"Pringle","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa012","article-title":"Progenitor cell niche senescence reflects pathology of the parotid salivary gland in primary sj\u00f6gren's syndrome","volume":"59","author":"Wang","year":"2020","journal-title":"Rheumatology"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2784","article-title":"A complex secretory program orchestrated by the inflammasome controls paracrine senescence","volume":"15","author":"Acosta","year":"2013","journal-title":"Nat Cell Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052302","article-title":"Chemokines up-regulated in epithelial cells control senescence-associated T cell accumulation in salivary glands of aged and sj\u00f6gren's syndrome model mice","volume":"22","author":"Kurosawa","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1002\/art.1780400113","article-title":"Fas and fas ligand expression in the salivary glands of patients with primary sj\u00f6gren's syndrome","volume":"40","author":"Kong","year":"1997","journal-title":"Arthritis Rheumatol"},{"key":"B40","article-title":"Quantitative analysis of apoptosis and bcl-2 in sj\u00f6gren's syndrome","volume":"24","author":"Manganelli","year":"1997","journal-title":"J Rheumatol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1998.4556","article-title":"Bcl-2 family expression in salivary glands from patients with primary sj\u00f6gren's syndrome: Involvement of bax in salivary gland destruction","volume":"88","author":"Kong","year":"1998","journal-title":"Clin Immunol Immunopathol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12638","article-title":"Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro\/Sj\u00f6gren's syndrome-related antigen a (SSA) and La\/SSB in salivary gland epithelial cells","volume":"181","author":"Katsiougiannis","year":"2015","journal-title":"Clin Exp Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/cei.12432","article-title":"Toll-like receptor 3 stimulation promotes Ro52\/TRIM21 synthesis and nuclear redistribution in salivary gland epithelial cells, partially via type I interferon pathway","volume":"178","author":"Kyriakidis","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102878","article-title":"Interferon-\u03b3 induces immunoproteasomes and the presentation of MHC I-associated peptides on human salivary gland cells","volume":"9","author":"Arellano-Garcia","year":"2014","journal-title":"PloS One"},{"key":"B45","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1074\/jbc.M111.277046","article-title":"Class II MHC antigen expression on epithelial cells of salivary glands from patients with sj\u00f6gren's syndrome","volume":"5","author":"Franco","year":"1987","journal-title":"Clin Exp Rheumatol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2010.06.006","article-title":"Salivary gland epithelial cells (SGEC): Carriers of exquisite B7-2 (CD86) co-stimulatory molecules","volume":"35","author":"Kapsogeorgou","year":"2010","journal-title":"J Autoimmun"},{"key":"B47","article-title":"Toll-like receptor in salivary glands from patients with sj\u00f6gren's syndrome: Functional analysis by human salivary gland cell line","volume":"34","author":"Kawakami","year":"2007","journal-title":"J Rheumatol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1034\/j.1600-0722.2002.00152.x","article-title":"Establishment of a convenient system for the long-term culture and study of non-neoplastic human salivary gland epithelial cells","volume":"110","author":"Dimitriou","year":"2002","journal-title":"Eur J Oral Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.2002.01168.x","article-title":"CD40, CD154, bax and bcl-2 expression in sj\u00f6gren's syndrome salivary glands: A putative antiapoptotic role during its effector phases","volume":"56","author":"Ohlsson","year":"2002","journal-title":"Scand J Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.4.2898","article-title":"Identification of IL-18 and Th17 cells in salivary glands of patients with sj\u00f6gren's syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18","volume":"181","author":"Sakai","year":"2008","journal-title":"J Immunol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"R2","DOI":"10.1186\/ar3220","article-title":"Salivary glands of primary sj\u00f6gren's syndrome patients express factors vital for plasma cell survival","volume":"13","author":"Szyszko","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2581","article-title":"Epithelial CXCR3-b regulates chemokines bioavailability in normal, but not in sj\u00f6gren's syndrome, salivary glands","volume":"176","author":"Sfriso","year":"2006","journal-title":"J Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200102)44:2<408::AID-ANR60>3.0.CO;2-0","article-title":"\"Lymphoid\" chemokine messenger RNA expression by epithelial cells in the chronic inflammatory lesion of the salivary glands of sj\u00f6gren's syndrome patients: possible participation in lymphoid structure formation","volume":"44","author":"Xanthou","year":"2001","journal-title":"Arthritis Rheumatol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200212","article-title":"Dysregulation of NF-kB in glandular epithelial cells results in sj\u00f6gren's-like features","volume":"13","author":"Wang","year":"2018","journal-title":"PloS One"},{"key":"B55","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/j.1365-2249.2006.03311.x","article-title":"Expression of functional toll-like receptors by salivary gland epithelial cells: Increased mRNA expression in cells derived from patients with primary sj\u00f6gren's syndrome","volume":"147","author":"Spachidou","year":"2007","journal-title":"Clin Exp Immunol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"195ra96","DOI":"10.1126\/scitranslmed.300572","article-title":"NCR3\/NKp30 contributes to pathogenesis in primary sj\u00f6gren's syndrome","volume":"5","author":"Rusakiewicz","year":"2013","journal-title":"Sci Transl Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200111)44:11<2633::AID-ART443>3.0.CO;2-9","article-title":"Ectopic expression of the b cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in sj\u00f6gren's syndrome","volume":"44","author":"Amft","year":"2001","journal-title":"Arthritis Rheumatol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2010.06.010","article-title":"Salivary epithelial cells from sj\u00f6gren's syndrome patients are highly sensitive to anoikis induced by TLR-3 ligation","volume":"35","author":"Manoussakis","year":"2010","journal-title":"J Autoimmun"},{"key":"B59","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.152.11.5532","article-title":"Cytokine mRNA expression in salivary gland biopsies of sj\u00f6gren's syndrome","volume":"152","author":"Fox","year":"1994","journal-title":"J Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jaut.2013.11.003","article-title":"Differentiation of follicular helper T cells by salivary gland epithelial cells in primary sj\u00f6gren's syndrome","volume":"51","author":"Gong","year":"2014","journal-title":"J Autoimmun"},{"key":"B61","article-title":"Increased expression of interferon-\u03bb in minor salivary glands of patients with primary sj\u00f6gren's syndrome and its synergic effect with interferon-\u03b1 on salivary gland epithelial cells","volume":"36","author":"Ha","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00605-2","article-title":"Epithelial\u2013immune cell interplay in primary sj\u00f6gren syndrome salivary gland pathogenesis","volume":"17","author":"Verstappen","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-eular.284","article-title":"Op0079 salivary gland epithelial cells (SGECS) promote the differentiation of b cells","volume":"72","author":"Morva","year":"2013","journal-title":"Ann Rheum. Dis"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.5130","article-title":"CXCL13, CCL21, and CXCL12 expression in salivary glands of patients with sj\u00f6gren's syndrome and MALT lymphoma: Association with reactive and malignant areas of lymphoid organization","volume":"180","author":"Barone","year":"2008","journal-title":"J Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez072","article-title":"Aspirin triggered resolvin D1 reduces inflammation and restores saliva secretion in a sj\u00f6gren's syndrome mouse model","volume":"58","author":"Dean","year":"2019","journal-title":"Rheumatol (Oxford)"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1559","article-title":"Human mesenchymal stem cells modulate allogeneic immune cell responses","volume":"105","author":"Aggarwal","year":"2005","journal-title":"Blood"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2020.09.008","article-title":"Minor salivary gland mesenchymal stromal cells derived from patients with Sj\u00f6;gren's syndrome deploy intact immune plasticity","volume":"23","author":"McCoy","year":"2021","journal-title":"Cytotherapy"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1365-2567.2004.02075.x","article-title":"How do follicular dendritic cells interact intimately with b cells in the germinal centre","volume":"114","author":"Park","year":"2005","journal-title":"Immunology"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2009.10.004","article-title":"Characteristics of the minor salivary gland infifiltrates in sj\u00f6gren's syndrome","volume":"34","author":"Christodoulou","year":"2010","journal-title":"J Autoimmun"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/art.23073","article-title":"Rates of infifiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflflammatory lesions of sj\u00f6gren's syndrome: Correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development","volume":"56","author":"Manoussakis","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102439","article-title":"Gene expression profifiling of epithelium-associated Fcrl4+ b cells in primary sj\u00f6gren's syndrome reveals a pathogenic signature","volume":"109","author":"Verstappen","year":"2020","journal-title":"J Autoimmun"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041919","article-title":"Early covert appearance of marginal zone b cells in salivary glands of sj\u00f6gren's syndrome-susceptible mice: Initiators of subsequent overt clinical disease","volume":"22","author":"Peck","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2016.04.008","article-title":"Central role for marginal zone b cells in an animal model of sj\u00f6gren's syndrome","volume":"168","author":"Shen","year":"2016","journal-title":"Clin Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/art.21936","article-title":"Identifification of transitional type II b cells in the salivary glands of patients with sj\u00f6gren\u2019s syndrome","volume":"54","author":"Daridon","year":"2006","journal-title":"Arthritis Rheum"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/art.10445","article-title":"Diminished peripheral blood memory b cells and accumulation of memory b cells in the salivary glands of patients with sj\u00f6gren's syndrome","volume":"46","author":"Hansen","year":"2002","journal-title":"Arthritis Rheum"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1002\/art.21129","article-title":"Dysregulation of chemokine receptor expression and function by b cells of patients with primary sj\u00f6gren's syndrome","volume":"52","author":"Hansen","year":"2005","journal-title":"Arthritis Rheum"},{"key":"B77","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/ar2210","article-title":"B cells in sj\u00f6gren's syndrome: Indications for disturbed selection and differentiation in ectopic lymphoid tissue","volume":"9","author":"Hansen","year":"2007","journal-title":"Arthritis Res Ther"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2019.1684475","article-title":"Autoantigen-specific b cells and plasma cells are prominent in areas of fatty infiltration in salivary glands of patients with primary sj\u00f6gren's syndrome","volume":"52","author":"Skarstein","year":"2019","journal-title":"Autoimmunity"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15613","article-title":"Investigation of three potential autoantibodies in sjogren's syndrome and associated MALT lymphoma","volume":"8","author":"Cui","year":"2017","journal-title":"Oncotarget"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.05.019","article-title":"The T cell in sjogren's syndrome: Force majeure, not spectateur","volume":"39","author":"Singh","year":"2012","journal-title":"J Autoimmun"},{"key":"B81","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaut.2017.11.003","article-title":"Th17 cells in primary sj\u00f6gren's syndrome: Pathogenicity and plasticity","volume":"87","author":"Verstappen","year":"2018","journal-title":"J Autoimmun"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez268","article-title":"Epigenetically quantified immune cells in salivary glands of sj\u00f6gren's syndrome patients: A novel tool that detects robust correlations of T follicular helper cells with immunopathology","volume":"59","author":"Blokland","year":"2020","journal-title":"Rheumatol (Oxford)"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217646","article-title":"Unique expansion of IL-21+ tfh and tph cells under control of ICOS identifies sj\u00f6gren's syndrome with ectopic germinal centres and MALT lymphoma, Ann","volume":"79","author":"Pontarini","year":"2020","journal-title":"Rheumatol Dis"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 t cells (TFH), annu","volume":"29","author":"Crotty","year":"2011","journal-title":"Rev Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.023","article-title":"ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6","volume":"34","author":"Choi","year":"2011","journal-title":"Immunity"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302617","article-title":"B cells in T follicular helper cell development and function: separable roles in delivery of ICOS ligand and antigen","volume":"192","author":"Weinstein","year":"2014","journal-title":"J Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12411","article-title":"T Follicular regulatory cells","volume":"271","author":"Sage","year":"2016","journal-title":"Immunol Rev"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810","article-title":"Pathologically expanded peripheral T helper cell subset drives b cells in rheumatoid arthritis","volume":"542","author":"Rao","year":"2017","journal-title":"Nature"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2020-001442","article-title":"Association between T follicular helper cells and T peripheral helper cells with b-cell biomarkers and disease activity in primary sj\u00f6gren syndrome","volume":"7","author":"Dupr\u00e9","year":"2021","journal-title":"RMD Open"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217646","article-title":"Unique expansion of IL-21+ tfh and tph cells under control of ICOS identifies sj\u00f6gren's syndrome with ectopic germinal centres and MALT lymphoma","volume":"79","author":"Pontarini","year":"2020","journal-title":"Ann Rheum. Dis"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/370650a0","article-title":"Cytolytic T-cell cytotoxicity is mediated through perforin and fas lytic pathways","volume":"370","author":"Lowin","year":"1994","journal-title":"Nature"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2021.166302","article-title":"Plasmacytoid dendritic cells promote the pathogenesis of sj\u00f6gren's syndrome","volume":"1868","author":"Zhou","year":"2022","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.04071.x","article-title":"Decrease of blood dendritic cells and increase of tissue-infiltrating dendritic cells are involved in the induction of sj\u00f6gren's syndrome but not in the maintenance","volume":"159","author":"Ozaki","year":"2010","journal-title":"Clin Exp Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002515","article-title":"Topological small-world organization of the fibroblastic reticular cell network determines lymph node functionality","volume":"14","author":"Novkovic","year":"2016","journal-title":"PloS Biol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1905301116","article-title":"Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology","volume":"116","author":"Nayar","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B96","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.medj.2022.05.002","article-title":"Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases","volume":"3","author":"Korsunsky","year":"2022","journal-title":"Med (N Y)"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.01.004","article-title":"Autocrine loop involving IL-6 family member LIF, LIF receptor, and STAT4 drives sustained fibroblast production of inflammatory mediators","volume":"46","author":"Nguyen","year":"2017","journal-title":"Immunity"},{"key":"B98","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s11882-018-0817-3","article-title":"Danger-associated molecular patterns (DAMPs): The derivatives and triggers of inflammation","volume":"18","author":"Patel","year":"2018","journal-title":"Curr Allergy Asthma Rep"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez316","article-title":"Aberrant MUC1 accumulation in salivary glands of sj\u00f6gren's syndrome patients is reversed by TUDCA in vitro","volume":"59","author":"Castro","year":"2020","journal-title":"Rheumatol (Oxford)"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.619304","article-title":"Complexity of danger: The diverse nature of damage-associated molecular patterns","volume":"289","author":"Schaefer","year":"2014","journal-title":"J Biol Chem"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/672395","article-title":"DAMPening inflammation by modulating TLR signalling","volume":"2010","author":"Piccinini","year":"2010","journal-title":"Mediators Inflflamm"},{"key":"B102","doi-asserted-by":"publisher","first-page":"roac034","DOI":"10.1093\/mr\/roac034","article-title":"The aberrant levels of decorin induce damages of human salivary gland epithelial cells and polarization of macrophages","author":"Gao","year":"2022","journal-title":"Mod. Rheumatol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.11","article-title":"The development and function of mucosal lymphoid tissues: A balancing act with micro-organisms","volume":"7","author":"TD","year":"2014","journal-title":"Mucosal Immunol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jaut.2014.02.008","article-title":"Infection and autoimmunity in sj\u00f6gren's syndrome: A clinical study and comprehensive review","volume":"51","author":"Kivity","year":"2014","journal-title":"J Autoimmun"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.891439","article-title":"B-cell hyperactivity in primary sj\u00f6gren's syndrome","volume":"10","author":"Kroese","year":"2014","journal-title":"Expert Rev Clin Immunol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1002\/art.10577","article-title":"Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with sj\u00f6gren's syndrome","volume":"46","author":"Ogawa","year":"2002","journal-title":"Arthritis Rheumatol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.217","article-title":"Ectopic lymphoid neogenesis in rheumatic autoimmune diseases","volume":"13","author":"Bombardieri","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/nri1151","article-title":"Lymphotoxin\/light, lymphoid microenvironments and autoimmune disease","volume":"3","author":"Gommerman","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/s1471-4906(01)02086-5","article-title":"Death-receptor contribution to the germinal-center reaction","volume":"22","author":"van Eijk","year":"2001","journal-title":"Trends Immunol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020437","article-title":"The inducible CXCR3 ligands control plasmacytoid dendritic cell responsiveness to the constitutive chemokine stromal cell-derived factor 1 (SDF-1)\/CXCL12","volume":"198","author":"Vanbervliet","year":"2003","journal-title":"J Exp Med"},{"key":"B111","doi-asserted-by":"publisher","first-page":"101547","DOI":"10.1016\/j.smim.2021.101547","article-title":"Cellular and molecular diversity in sjogren's syndrome salivary glands: Towards a better definition of disease subsets","author":"Pontarini","year":"2021","journal-title":"Semin Immunol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxab025","article-title":"Sj\u00f6gren's syndrome-associated SNPs increase GTF2I expression in salivary gland cells to enhance inflammation development","volume":"33","author":"Shimoyama","year":"2021","journal-title":"Int Immunol"},{"key":"B113","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13075-020-02248-2","article-title":"Identification of novel genes associated with dysregulation of b cells in patients with primary sj\u00f6gren's syndrome","volume":"22","author":"Inamo","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00290","article-title":"Interferons in sj\u00f6gren's syndrome: genes, mechanisms, and effects","volume":"4","author":"Li","year":"2013","journal-title":"Front Immunol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102867","article-title":"Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in sj\u00f6gren's syndrome","volume":"20","author":"Barrera","year":"2021","journal-title":"Autoimmun. Rev"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.845209","article-title":"A link between mitochondrial dysfunction and the immune microenvironment of salivary glands in primary sj\u00f6gren's syndrome","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2022.2062593","article-title":"Contribution of DNA methylation to the pathogenesis of sj\u00f6gren's syndrome: A review","volume":"55","author":"Guimar\u00e3es","year":"2022","journal-title":"Autoimmunity"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2013.02.002","article-title":"Epigenetic dysregulation in salivary glands from patients with primary sj\u00f6gren's syndrome may be ascribed to infiltrating b cells","volume":"41","author":"Thabet","year":"2013","journal-title":"J Autoimmun"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.870094","article-title":"Small RNA expression profiling reveals hsa-miR-181d-5p downregulation associated with TNF-\u03b1 overexpression in sj\u00f6gren's syndrome patients","volume":"13","author":"Castro","year":"2022","journal-title":"Front Immunol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.875341","article-title":"Blood HDAC4 variation links with disease activity and response to tumor necrosis factor inhibitor and regulates CD4+ T cell differentiation in ankylosing spondylitis","volume":"9","author":"Dou","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"B121","doi-asserted-by":"publisher","first-page":"10513","DOI":"10.1038\/s41598-022-14052-w","article-title":"HDAC6 is a prognostic biomarker that mediates IL-13 expression to regulate macrophage polarization through AP-1 in oral squamous cell carcinoma","volume":"12","author":"Tseng","year":"2022","journal-title":"Sci Rep"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00874-1","article-title":"The deacetylase SIRT2 contributes to autoimmune disease pathogenesis by modulating IL-17A and IL-2 transcription","volume":"19","author":"Hisada","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.03.002","article-title":"Controlled release of an HDAC inhibitor for reduction of inflammation in dry eye disease","volume":"71","author":"Ratay","year":"2018","journal-title":"Acta Biomater"},{"key":"B124","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.molimm.2022.05.004","article-title":"HDAC6-specific inhibitor alleviates hashimoto's thyroiditis through inhibition of Th17 cell differentiation","volume":"149","author":"Chang","year":"2022","journal-title":"Mol Immunol"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-07065-7","article-title":"Trichostatin a inhibits dendritic cell maturation through down-regulating NF-\u03ba b (p65) pathway","volume":"49","author":"Yu","year":"2022","journal-title":"Mol Biol Rep"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.151713","article-title":"Plasma cell dependence on histone\/protein deacetylase 11 reveals a therapeutic target in multiple myeloma","volume":"6","author":"Mostofa","year":"2021","journal-title":"JCI Insight"},{"key":"B127","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1002\/path.1533","article-title":"Expression of BAFF (BLyS) in T cells infiltrating labial salivary glands from patients with sj\u00f6gren's syndrome","volume":"202","author":"Lavie","year":"2004","journal-title":"J Pathol"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1002\/art.22458","article-title":"Aberrant expression of BAFF by b lymphocytes infiltrating the salivary glands of patients with primary sj\u00f6gren's syndrome","volume":"56","author":"Daridon","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2014.02.004","article-title":"Specific forms of BAFF favor BAFF receptor-mediated epithelial cell survival","volume":"51","author":"Lahiri","year":"2014","journal-title":"J Autoimmun"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1038\/ni829","article-title":"DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL","volume":"3","author":"Litinskiy","year":"2002","journal-title":"Nat Immunol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501061","article-title":"The expression of BAFF is controlled by IRF transcription factors","volume":"196","author":"Sj\u00f6strand","year":"2016","journal-title":"J Immunol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511794112","article-title":"Erlotinib protects against LPS-induced endotoxicity because TLR4 needs EGFR to signal","volume":"112","author":"De","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002581","article-title":"Epidermal growth factor receptor is essential for toll-like receptor 3 signaling","volume":"5","author":"Yamashita","year":"2012","journal-title":"Sci Signal"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.100","article-title":"Toll-like receptor 4 differentially regulates epidermal growth factor-related growth factors in response to intestinal mucosal injury","volume":"90","author":"Hsu","year":"2010","journal-title":"Lab Invest"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-013-9487-6","article-title":"Salivary gland expression level of I\u03baB\u03b1 regulatory protein in sj\u00f6gren's syndrome","volume":"44","author":"Sisto","year":"2013","journal-title":"J Mol Histol"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-007-0411-9","article-title":"EGF activates PI3K-akt and NF-\u03baB via distinct pathways in salivary epithelial cells in sj\u00f6gren's syndrome","volume":"28","author":"Nakamura","year":"2007","journal-title":"Rheumatol. Int"},{"key":"B137","doi-asserted-by":"publisher","first-page":"R64","DOI":"10.1186\/ar3780","article-title":"TLR2 ligation induces the production of IL-23\/IL-17 via IL-6, STAT3 and NF-kB pathway in patients with primary sj\u00f6gren's syndrome","volume":"14","author":"Kwok","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-016-0429-y","article-title":"TLR2 signals via NF-\u03baB to drive IL-15 production in salivary gland epithelial cells derived from patients with primary sj\u00f6gren's syndrome","volume":"17","author":"Sisto","year":"2017","journal-title":"Clin Exp Med"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12765","article-title":"Upregulation of IL-6 expression in human salivary gland cell line by IL-17 via activation of p38 MAPK, ERK, PI3K\/Akt, and NF-\u03baB pathways","volume":"47","author":"Wei","year":"2018","journal-title":"J Oral Pathol Med"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B141","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.5","article-title":"TGF-beta-induced epithelial to mesenchymal transition","volume":"19","author":"Xu","year":"2009","journal-title":"Cell Res"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1965935","article-title":"The TGF-\u03b21 signaling pathway as an attractive target in the fibrosis pathogenesis of sj\u00f6gren's syndrome","volume":"2018","author":"Sisto","year":"2018","journal-title":"Mediators Inflamm"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13337","article-title":"Interleukin-17 and -22 synergy linking inflammation and EMT-dependent fibrosis in sj\u00f6gren's syndrome","volume":"198","author":"Sisto","year":"2019","journal-title":"Clin Exp Immunol"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302339200","article-title":"Interferon-gamma interferes with transforming growth factor-beta signaling through direct interaction of YB-1 with SMAD3","volume":"278","author":"Higashi","year":"2003","journal-title":"J Biol Chem"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1038\/17826","article-title":"Inhibition of transforming growth factor-\u03b2\/SMAD signalling by the interferon-\u03b3\/STAT pathway","volume":"397","author":"Ulloa","year":"1999","journal-title":"Nature"},{"key":"B147","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0165-2478(02)00023-8","article-title":"Mechanisms of TGF-\u03b2signaling in regulation of cell growth and differentiation","volume":"82","author":"Moustakas","year":"2002","journal-title":"Immunol Lett"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510837103","article-title":"Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary sj\u00f6gren's syndrome","volume":"103","author":"Gottenberg","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1002\/art.21006","article-title":"Gene expression profifiling of minor salivary glands clearly distinguishes primary sj\u00f6gren's syndrome patients from healthy control subjects","volume":"52","author":"Hjelmervik","year":"2005","journal-title":"Arthritis Rheumatol"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1002\/art.39204","article-title":"Molecular subsetting of interferon pathways in sj\u00f6gren's syndrome","volume":"67","author":"Hall","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12865","article-title":"Expression of type III interferons (IFN\u03bbs) and their receptor in sj\u00f6gren's syndrome","volume":"186","author":"Apostolou","year":"2016","journal-title":"Clin Exp Immunol"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1002\/art.38123","article-title":"Association of bone morphogenetic protein 6 with exocrine gland dysfunction in patients with sj\u00f6gren's syndrome and in mice","volume":"65","author":"Yin","year":"2013","journal-title":"Arthritis Rheumatol"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1172\/JCI152780","article-title":"Lysosomal exocytosis of HSP70 stimulates monocytic BMP6 expression in sj\u00f6gren's syndrome","volume":"132","author":"Mo","year":"2022","journal-title":"J Clin Invest"},{"key":"B154","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.3390\/ijms19061801","article-title":"Role of human macrophage polarization in inflammation during infectious diseases","volume":"19","author":"Atri","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.1860070309","article-title":"Expression of cell adhesion molecules in the salivary and lacrimal glands of sj\u00f6gren's syndrome","volume":"7","author":"Saito","year":"1993","journal-title":"J Clin Lab Anal"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2021.151865","article-title":"Specialized pro-resolving receptors are expressed in salivary glands with sj\u00f6gren's syndrome","volume":"56","author":"Dos Santos","year":"2022","journal-title":"Ann Diagn Pathol"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00207.2011","article-title":"Resolvin D1 prevents TNF-\u03b1- mediated disruption of salivary epithelial formation","volume":"302","author":"Odusanwo","year":"2012","journal-title":"Am J Physiol Cell Physiol"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902196R","article-title":"Sex-mediated elevation of the specialized pro-resolving lipid mediator levels in a sj\u00f6gren's syndrome mouse model","volume":"34","author":"Parashar","year":"2020","journal-title":"FASEB J"},{"key":"B159","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jaut.2013.02.001","article-title":"Sj\u00f6gren's syndrome and the epithelial target: A comprehensive review, J","volume":"42","author":"Barrera","year":"2013","journal-title":"Autoimmun"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110042","article-title":"CTRP3 promotes TNF-\u03b1-induced apoptosis and barrier dysfunction in salivary epithelial cells","volume":"85","author":"Mei","year":"2021","journal-title":"Cell Signal"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30262","article-title":"C1q\/tumor necrosis factor-related protein-6 attenuates TNF-\u03b1-induced apoptosis in salivary acinar cells via AMPK\/SIRT1-modulated miR-34a-5p expression","volume":"236","author":"Qu","year":"2021","journal-title":"J Cell Physiol"},{"key":"B162","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s13075-022-02769-y","article-title":"Impaired activation of STAT5 upon IL-2 stimulation in tregs and elevated sIL-2R in sj\u00f6gren's syndrome","volume":"24","author":"Keindl","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1177\/0394632016651273","article-title":"A case for IL-6, IL-17A, and nitric oxide in the pathophysiology of sj\u00f6gren's syndrome","volume":"29","author":"Benchabane","year":"2016","journal-title":"Int J Immunopathol Pharmacol"},{"key":"B164","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00005-020-00591-5","article-title":"IL-6 contributes to the TGF-\u03b21-Mediated epithelial to mesenchymal transition in human salivary gland epithelial cells","volume":"68","author":"Sisto","year":"2020","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1002\/art.27318","article-title":"Increased expression of interleukin-7 in labial salivary glands of patients with primary sj\u00f6gren's syndrome correlates with increased inflammation","volume":"62","author":"Bikker","year":"2010","journal-title":"Arthritis Rheumatol"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1002\/art.40182","article-title":"Increased CCL25 and T helper cells expressing CCR9 in the salivary glands of patients with primary sj\u00f6gren's syndrome: Potential new axis in lymphoid neogenesis","volume":"69","author":"Blokland","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090319","article-title":"Systemic and local interleukin-17 and linked cytokines associated with sj\u00f6gren's syndrome immunopathogenesis","volume":"175","author":"Katsifis","year":"2009","journal-title":"Am J Pathol"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1277","article-title":"IL-17 drives salivary gland dysfunction via inhibiting TRPC1-mediated calcium movement in sj\u00f6gren's syndrome","volume":"10","author":"Xiao","year":"2021","journal-title":"Clin Transl Immunol"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003871","article-title":"IL-21 receptor is required for the systemic accumulation of activated b and T lymphocytes in MRL\/MpJ-Fas(lpr\/lpr)\/J mice","volume":"188","author":"Rankin","year":"2012","journal-title":"J Immunol"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.06.068","article-title":"Loss of prolyl hydroxylase-1 protects against colitis through reduced epithelial cell apoptosis and increased barrier function","volume":"139","author":"Tambuwala","year":"2010","journal-title":"Gastroenterology"},{"key":"B171","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1053\/j.gastro.2007.10.012","article-title":"The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis","volume":"134","author":"Cummins","year":"2008","journal-title":"Gastroenterology"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.09.033","article-title":"Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition","volume":"134","author":"Robinson","year":"2008","journal-title":"Gastroenterology"},{"key":"B173","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1159\/000430225","article-title":"The effect and mechanism of celecoxib in hypoxia-induced survivin up-regulation in HUVECs","volume":"37","author":"Liu","year":"2015","journal-title":"Cell Physiol Biochem"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1159\/000485764","article-title":"Celecoxib down-regulates the hypoxia-induced expression of HIF-1\u03b1 and VEGF through the PI3K\/AKT pathway in retinal pigment epithelial cells","volume":"44","author":"Sun","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0092-9","article-title":"Senolytics improve physical function and increase lifespan in old age","volume":"24","author":"Xu","year":"2018","journal-title":"Nat Med"},{"key":"B176","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41467-017-00314-z","article-title":"Identification of HSP90 inhibitors as a novel class of senolytics","volume":"8","author":"Fuhrmann-Stroissnigg","year":"2017","journal-title":"Nat Commun"},{"key":"B177","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1038\/s41419-020-03074-9","article-title":"Cellular senescence contributes to radiation-induced hyposalivation by affecting the stem\/progenitor cell niche","volume":"11","author":"Peng","year":"2020","journal-title":"Cell Death Dis"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.7150\/thno.23373","article-title":"Delivery of sonic hedgehog gene repressed irradiation-induced cellular senescence in salivary glands by promoting DNA repair and reducing oxidative stress","volume":"8","author":"Hai","year":"2018","journal-title":"Theranostics"},{"key":"B179","article-title":"Persistence of focal lymphocytic sialadenitis in patients with primary sj\u00f6gren's syndrome treated with rituximab: A possible role for glandular BAFF","volume":"34","author":"Carubbi","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"B180","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1158\/0008-5472.CAN-15-1671","article-title":"Radiation-induced loss of salivary gland function is driven by cellular senescence and prevented by IL6 modulation","volume":"76","author":"Marmary","year":"2016","journal-title":"Cancer Res"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218467","article-title":"Interleukin 6 receptor inhibition in primary sj\u00f6gren syndrome: A multicentre double-blind randomised placebo-controlled trial","volume":"80","author":"Felten","year":"2021","journal-title":"Ann Rheum. Dis"},{"key":"B182","doi-asserted-by":"publisher","first-page":"bcr2014209076","DOI":"10.1136\/bcr-2014-209076","article-title":"Tocilizumab for refractory organising pneumonia associated with sj\u00f6gren's disease","volume":"2015","author":"Justet","year":"2015","journal-title":"BMJ Case Rep"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016285","article-title":"Refractory sj\u00f6gren's syndrome myelopathy successfully treated with subcutaneous tocilizumab: A case report","volume":"98","author":"Ishikawa","year":"2019","journal-title":"Med (Baltimore)"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/356040","article-title":"Regulatory effect of iguratimod on the balance of Th subsets and inhibition of inflammatory cytokines in patients with rheumatoid arthritis","volume":"2015","author":"Xu","year":"2015","journal-title":"Mediators Inflamm"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1080\/03009742.2020.1809701","article-title":"Efficacy and safety of iguratimod on patients with primary sj\u00f6gren's syndrome: A randomized, placebo-controlled clinical trial","volume":"50","author":"Shao","year":"2021","journal-title":"Scand J Rheumatol"},{"key":"B186","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1000-484X.2021.08.003","article-title":"Effects of iramod on submandibular gland inflammation and NF-\u03baB signaling pathway in sj\u00f6gren's syndrome mice","volume":"37","author":"Qi","year":"2021","journal-title":"Chin J Immunol"},{"key":"B187","doi-asserted-by":"publisher","first-page":"R172","DOI":"10.1186\/ar4359","article-title":"Effificacy and safety of rituximab treatment in early primary sj\u00f6gren's syndrome: A prospective, multi-center, follow-up study","volume":"15","author":"Carubbi","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"B188","article-title":"Double anti-B cell and anti-BAFF targeting for the treatment of primary Sj\ufffdgren's syndrome","volume-title":"Clin Exp Rheumatol","author":"Gandolfo","year":"2019"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.817","article-title":"Importance of cellular microenvironment and circulatory dynamics in b cell immunotherapy","volume":"174","author":"Gong","year":"2005","journal-title":"J Immunol"},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1080\/08916930400002386","article-title":"The role of CD40\u2013CD154 interactions in autoimmunity and the benefit of disrupting this pathway","volume":"37","author":"Toubi","year":"2004","journal-title":"Autoimmunity"},{"key":"B191","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214720","article-title":"Treatment of primary sj\u00f6gren's syndrome with ianalumab (VAY736) targeting b cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity","volume":"78","author":"D\u00f6rner","year":"2019","journal-title":"Ann Rheum. Dis"},{"key":"B192","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.871096","article-title":"Labial gland mesenchymal stem cell derived exosomes-mediated miRNA-125b attenuates experimental sj\u00f6gren's syndrome by targeting PRDM1 and suppressing plasma cells","volume":"13","author":"Xing","year":"2022","journal-title":"Front Immunol"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.16.5214","article-title":"Cyclosporin a inhibits T-cell growth factor gene expression at the level of mRNA transcription","volume":"81","author":"Kronke","year":"1984","journal-title":"Proc Natl Acad Sci USA"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199311000-00008","article-title":"Effect of topical cyclosporin a on conjunctival T cells in patients with secondary sj\u00f6gren's syndrome","volume":"12","author":"Power","year":"1993","journal-title":"Cornea"},{"key":"B195","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev257","article-title":"Efficacy and safety of belimumab given for 12 months in primary sj\u00f6gren's syndrome: The BELISS open-label phase II study","volume":"54","author":"De Vita","year":"2015","journal-title":"Rheumatol (Oxford)"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.11.3460","article-title":"Hydroxychloroquine inhibits calcium signals in T cells: A new mechanism to explain its immunomodulatory properties","volume":"95","author":"Goldman","year":"2000","journal-title":"Blood"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2014.951144","article-title":"Efficacy and safety of abatacept for patients with sj\u00f6gren's syndrome associated with rheumatoid arthritis: Rheumatoid arthritis with orencia trial toward sj\u00f6gren's syndrome endocrinopathy (ROSE) trial\u2013an open-label, one-year, prospective study\u2013interim analysis of 32 patients for 24 weeks","volume":"25","author":"Tsuboi","year":"2015","journal-title":"Mod. Rheumatol"},{"key":"B198","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2022.151955","article-title":"Long-term abatacept treatment for 48 weeks in patients with primary sj\u00f6gren's syndrome: The open-label extension phase of the ASAP-III trial","volume":"53","author":"de Wolff","year":"2022","journal-title":"Semin Arthritis Rheumatol"},{"key":"B199","article-title":"Abatacept treatment of patients with primary sj\u00f6gren's syndrome results in a decrease of germinal centres in salivary gland tissue, clin","volume":"35","author":"Haacke","year":"2017","journal-title":"Exp Rheumatol"},{"key":"B200","doi-asserted-by":"publisher","DOI":"10.1002\/art.40165","article-title":"Attenuation of follicular helper T cell-dependent b cell hyperactivity by abatacept treatment in primary sj\u00f6gren's syndrome, arthritis rheumatol","volume":"69","author":"Verstappen","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"B201","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204653","article-title":"Abatacept treatment reduces disease activity in early primary sj\u00f6gren's syndrome (open-label proof of concept ASAP study)","volume":"73","author":"Meiners","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"B202","article-title":"Blocking T cell co-stimulation in primary Sj\u00f6gren's syndrome: Rationale, clinical efficacy and modulation of peripheral and salivary gland biomarkers","volume":"126","author":"Pontarini","year":"2020","journal-title":"Clin Exp Rheumatol"},{"key":"B203","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120182","article-title":"Blocking IAg7 class II major histocompatibility complex by drug-like small molecules alleviated sj\u00f6gren's syndrome in NOD mice","volume":"288","author":"Gupta","year":"2022","journal-title":"Life Sci"},{"key":"B204","article-title":"Prednisone and piroxicam for treatment of primary sj\u00f6gren's syndrome","volume":"11","author":"Fox","year":"1993","journal-title":"Clin Exp Rheumatol"},{"key":"B205","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.052647","article-title":"Progression of salivary gland dysfunction in patients with sj\u00f6gren's syndrome","volume":"66","author":"Pijpe","year":"2006","journal-title":"Ann Rheum Dis"},{"key":"B206","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1042\/bj3360299","article-title":"Purification of human dihydroorotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomide","volume":"336","author":"Bruneau","year":"1998","journal-title":"Biochem J"},{"key":"B207","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.162.4.2095","article-title":"Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa b activation and gene expression","volume":"162","author":"Manna","year":"1999","journal-title":"J Immunol"},{"key":"B208","doi-asserted-by":"crossref","DOI":"10.1136\/ard.2006.060905","article-title":"Safety and efficacy of leflunomide in primary sj\u00f6gren's syndrome: A phase II pilot study","volume":"66","author":"van Woerkom","year":"2007","journal-title":"Ann Rheum. Dis"},{"key":"B209","doi-asserted-by":"publisher","DOI":"10.1177\/0961203396005001081","article-title":"Treatment of primary sj\u00f6gren's syndrome with hydroxychloroquine: A retrospective, open-label study","volume":"5","author":"Fox","year":"1996","journal-title":"Lupus"},{"key":"B210","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.7682","article-title":"Effects of hydroxychloroquine on symptomatic improvement in primary sj\u00f6gren syndrome: The JOQUER randomized clinical trial","volume":"312","author":"Gottenberg","year":"2014","journal-title":"JAMA"},{"key":"B211","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.imlet.2020.07.005","article-title":"Injection of CD40 DNA vaccine ameliorates the autoimmune pathology of non-obese diabetic mice with sj\u00f6gren's syndrome","volume":"226","author":"Zhou","year":"2020","journal-title":"Immunol Lett"},{"key":"B212","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15661","article-title":"First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody","volume":"20","author":"Espi\u00e9","year":"2020","journal-title":"Am J Transplant"},{"key":"B213","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.04.010","article-title":"Anti-IL-7 receptor-\u03b1 treatment ameliorates newly established sj\u00f6gren's-like exocrinopathy in non-obese diabetic mice","volume":"1864","author":"Zhou","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B214","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13748","article-title":"Anti-IL-7 receptor \u03b1 monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study","volume":"85","author":"Ellis","year":"2019","journal-title":"Br J Clin Pharmacol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.967304\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T22:41:25Z","timestamp":1676760085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.967304\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":214,"alternative-id":["10.3389\/fimmu.2022.967304"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.967304","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]},"article-number":"967304"}}