{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:03:05Z","timestamp":1792789385176,"version":"4.5.0"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T00:00:00Z","timestamp":1518480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NEI","award":["EY026893"],"award-info":[{"award-number":["EY026893"]}]},{"name":"Alkek Center for Metagenomics and Microbiome Research"},{"name":"Biology of Inflammation Center"},{"name":"NIH Trainining grant","award":["T32-AI053831"],"award-info":[{"award-number":["T32-AI053831"]}]},{"DOI":"10.13039\/100001818","name":"RPB","doi-asserted-by":"publisher","award":["Stein Innovation Award"],"award-info":[{"award-number":["Stein Innovation Award"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Oshman Foundation"},{"name":"William Stamps Farish Fund"},{"DOI":"10.13039\/100017017","name":"The Hamill Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017017","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH NIAID","award":["P30AI036211"],"award-info":[{"award-number":["P30AI036211"]}]},{"name":"NIH NCI","award":["P30CA125123"],"award-info":[{"award-number":["P30CA125123"]}]},{"name":"NIH NCRR","award":["S10RR024574"],"award-info":[{"award-number":["S10RR024574"]}]},{"name":"Zhejiang Provincial Medical and Health Science and Technology Program","award":["2015KYA113"],"award-info":[{"award-number":["2015KYA113"]}]},{"name":"Zhejiang Key Laboratory Fund of China","award":["2011E10006"],"award-info":[{"award-number":["2011E10006"]}]},{"DOI":"10.13039\/100001315","name":"Sid W. Richardson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Commensal bacteria play an important role in the formation of the immune system but their role in the maintenance of immune homeostasis at the ocular surface and lacrimal gland remains poorly understood. This study investigated the eye and lacrimal gland phenotype in germ-free and conventional C57BL\/6J mice. Our results showed that germ-free mice had significantly greater corneal barrier disruption, greater goblet cell loss, and greater total inflammatory cell and CD4+ T cell infiltration within the lacrimal gland compared to the conventionally housed group. A greater frequency of CD4+IFN-\u03b3+ cells was observed in germ-free lacrimal glands. Females exhibited a more severe phenotype compared to males. Adoptive transfer of CD4+ T cells isolated from female germ-free mice into RAG1KO mice transferred Sj\u00f6gren-like lacrimal keratoconjunctivitis. Fecal microbiota transplant from conventional mice reverted dry eye phenotype in germ-free mice and decreased CD4+IFN-\u03b3+ cells to levels similar to conventional C57BL\/6J mice. These findings indicate that germ-free mice have a spontaneous lacrimal keratoconjunctivitis similar to that observed in Sj\u00f6gren syndrome patients and demonstrate that commensal bacteria function in maintaining immune homeostasis on the ocular surface. Thus, manipulation of intestinal commensal bacteria has the potential to become a novel therapeutic approach to treat Sj\u00f6gren Syndrome.<\/jats:p>","DOI":"10.3390\/ijms19020565","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T14:23:48Z","timestamp":1518531828000},"page":"565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Sj\u00f6gren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice"],"prefix":"10.3390","volume":"19","author":[{"given":"Changjun","family":"Wang","sequence":"first","affiliation":[{"name":"Eye Institute of Zhejiang University School of Medicine, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310009, China"},{"name":"Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahira","family":"Zaheer","sequence":"additional","affiliation":[{"name":"Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Bian","sequence":"additional","affiliation":[{"name":"Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin","family":"Quach","sequence":"additional","affiliation":[{"name":"Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alton","family":"Swennes","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Britton","sequence":"additional","affiliation":[{"name":"Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Pflugfelder","sequence":"additional","affiliation":[{"name":"Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-5494","authenticated-orcid":false,"given":"Cintia","family":"De Paiva","sequence":"additional","affiliation":[{"name":"Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1136\/bjo.51.7.483","article-title":"Evaluation of conjunctival and nasal bacterial cultures before intra-ocular operations","volume":"51","author":"Nolan","year":"1967","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/j.1755-3768.1975.tb01178.x","article-title":"Bacterial flora in relation to cataract extraction. II. Peroperative flora","volume":"53","author":"Fahmy","year":"1975","journal-title":"Acta Ophthalmol."},{"key":"ref_3","first-page":"1164","article-title":"16S rDNA-based identification of bacteria from conjunctival swabs by PCR and DGGE fingerprinting","volume":"42","author":"Maca","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1167\/iovs.02-1301","article-title":"Expression of human \u03b2-defensins in conjunctival epithelium: Relevance to dry eye disease","volume":"44","author":"Narayanan","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1021\/pr034065n","article-title":"Proteomic analysis of human tears: Defensin expression after ocular surface surgery","volume":"3","author":"Zhou","year":"2004","journal-title":"J. Proteome Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exer.2013.07.014","article-title":"Antimicrobial compounds in tears","volume":"117","author":"McDermott","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1755-3768.1986.tb06877.x","article-title":"The concentration of lactoferrin in tears of normals and of diabetics","volume":"64","author":"Jensen","year":"1986","journal-title":"Acta Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1755-3768.1987.tb08485.x","article-title":"The concentration of lysozyme and secretory IgA in tears from healthy persons with and without contact lens use","volume":"65","author":"Vinding","year":"1987","journal-title":"Acta Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1136\/bjo.83.6.737","article-title":"Antimicrobial defensin peptides of the human ocular surface","volume":"83","author":"Haynes","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.exer.2013.06.003","article-title":"Characterization of the normal microbiota of the ocular surface","volume":"117","author":"Willcox","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.ajo.2014.06.014","article-title":"Considerations in understanding the ocular surface microbiome","volume":"158","author":"Zegans","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23561","DOI":"10.1038\/srep23561","article-title":"Altered Mucosal Microbiome Diversity and Disease Severity in Sjogren Syndrome","volume":"6","author":"Jones","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.cmi.2016.04.008","article-title":"Defining the normal \u201ccore microbiome\u201d of conjunctival microbial communities","volume":"22","author":"Huang","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5616","DOI":"10.1167\/iovs.07-0588","article-title":"Ocular pathogen or commensal: A PCR-based study of surface bacterial flora in normal and dry eyes","volume":"48","author":"Graham","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9880","DOI":"10.1038\/s41598-017-10494-9","article-title":"Temporal Stability and Composition of the Ocular Surface Microbiome","volume":"7","author":"Ozkan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.immuni.2017.06.014","article-title":"An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal \u03b3\u03b4 T Cells","volume":"47","author":"Desai","year":"2017","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kugadas, A., Christiansen, S.H., Sankaranarayanan, S., Surana, N.K., Gauguet, S., Kunz, R., Fichorova, R., Vorup-Jensen, T., and Gadjeva, M. (2016). Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005855"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jtos.2016.04.004","article-title":"Impact of Microbiome on Ocular Health","volume":"14","author":"Kugadas","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1167\/iovs.17-22119","article-title":"Role of Microbiota in Strengthening Ocular Mucosal Barrier Function through Secretory IgA","volume":"58","author":"Kugadas","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6734","DOI":"10.1038\/ncomms7734","article-title":"Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome","volume":"6","author":"Macia","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neulet.2016.02.009","article-title":"Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?","volume":"625","author":"Bourassa","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.pharmthera.2015.11.012","article-title":"Gut microbiome in health and disease: Linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases","volume":"158","author":"Ghaisas","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kigerl, K.A., Hall, J.C., Wang, L., Mo, X., Yu, Z., and Popovich, P.G. (2016). Gut dysbiosis impairs recovery after spinal cord injury. J. Exp. Med.","DOI":"10.1084\/jem.20151345"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Luczynski, P., McVey Neufeld, K.A., Oriach, C.S., Clarke, G., Dinan, T.G., and Cryan, J.F. (2016). Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior. Int. J. Neuropsychopharmacol., 19.","DOI":"10.1093\/ijnp\/pyw020"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/nature08530","article-title":"Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43","volume":"461","author":"Maslowski","year":"2009","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.clim.2015.05.008","article-title":"Control of intestinal homeostasis through crosstalk between natural killer T cells and the intestinal microbiota","volume":"159","author":"Dowds","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"137rv7","DOI":"10.1126\/scitranslmed.3004184","article-title":"Microbiota, disease, and back to health: A metastable journey","volume":"4","author":"Blumberg","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13293-015-0037-7","article-title":"Sex differences in Sjogren\u2019s syndrome: A comprehensive review of immune mechanisms","volume":"6","author":"Brandt","year":"2015","journal-title":"Biol. Sex Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0002-9394(03)00218-6","article-title":"Prevalence of dry eye syndrome among US women","volume":"136","author":"Schaumberg","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ajpath.2013.11.019","article-title":"Ocular Surface Disease and Dacryoadenitis in Aging C57BL\/6 Mice","volume":"184","author":"McClellan","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13075-015-0582-9","article-title":"Altered balance of interleukin-13\/interferon-\u03b3 contributes to lacrimal gland destruction and secretory dysfunction in CD25 knockout model of Sjogren\u2019s syndrome","volume":"17","author":"Bian","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1097\/00003226-199611000-00013","article-title":"Cholinergic stimulation of lactoferrin and epidermal growth factor secretion by the human lacrimal gland","volume":"15","author":"Yoshino","year":"1996","journal-title":"Cornea"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R234","DOI":"10.1186\/ar4077","article-title":"Deletion of interferon-\u03b3 delays onset and severity of dacryoadenitis in CD25KO mice","volume":"14","author":"Pelegrino","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/art.10258","article-title":"Two NOD Idd-associated intervals contribute synergistically to the development of autoimmune exocrinopathy (Sjogren\u2019s syndrome) on a healthy murine background","volume":"46","author":"Cha","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/154411130201300103","article-title":"Progress in understanding autoimmune exocrinopathy using the non-obese diabetic mouse: An update","volume":"13","author":"Cha","year":"2002","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_36","first-page":"426","article-title":"Conjunctival Goblet Cells modulate dendritic cell maturation and retinoic acid producing capacity","volume":"57","author":"Xiao","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Contreras-Ruiz, L., and Masli, S. (2015). Immunomodulatory cross-talk between conjunctival goblet cells and dendritic cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120284"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Barbosa, F.L., Xiao, Y., Bian, F., Coursey, T.G., Ko, B.Y., Clevers, H., de Paiva, C.S., and Pflugfelder, S.C. (2017). Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050978"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ajpath.2013.03.017","article-title":"Spdef null mice lack conjunctival goblet cells and provide a model of dry eye","volume":"183","author":"Marko","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.ajpath.2016.02.004","article-title":"Interferon-\u03b3-Induced Unfolded Protein Response in Conjunctival Goblet Cells as a Cause of Mucin Deficiency in Sjogren Syndrome","volume":"186","author":"Coursey","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/mi.2015.53","article-title":"Interaction of IFN-\u03b3 with cholinergic agonists to modulate rat and human goblet cell function","volume":"9","author":"Hodges","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1126\/science.1198469","article-title":"Induction of colonic regulatory T cells by indigenous Clostridium species","volume":"331","author":"Atarashi","year":"2011","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.4049\/jimmunol.176.7.3950","article-title":"Desiccating Stress Induces T Cell-Mediated Sjogren\u2019s Syndrome-Like Lacrimal Keratoconjunctivitis","volume":"176","author":"Niederkorn","year":"2006","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Coursey, T.G., Gandhi, N.B., Volpe, E.A., Pflugfelder, S.C., and de Paiva, C.S. (2013). Chemokine receptors CCR6 and CXCR3 are necessary for CD4+ T cell mediated ocular surface disease in experimental dry eye disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078508"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/mi.2016.83","article-title":"Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells","volume":"10","author":"Coursey","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1167\/iovs.07-0069","article-title":"Dry Eye-Induced Conjunctival Epithelial Squamous Metaplasia Is Modulated by Interferon-\u03b3","volume":"48","author":"Villarreal","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/mi.2010.82","article-title":"Homeostatic control of conjunctival mucosal goblet cells by NKT-derived IL-13","volume":"4","author":"Raince","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1538\/expanim1978.40.4_523","article-title":"Immunological function of food-restricted germfree and specific pathogen-free mice","volume":"40","author":"Tazume","year":"1991","journal-title":"Exp. Anim."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.4014\/jmb.1501.01039","article-title":"Use of Germ-Free Animal Models in Microbiota-Related Research","volume":"25","author":"Zadjali","year":"2015","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1538\/expanim.45.155","article-title":"Histochemical, lectin-histochemical and morphometrical characteristics of intestinal goblet cells of germfree and conventional mice","volume":"45","author":"Kandori","year":"1996","journal-title":"Exp. Anim."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jaut.2013.07.007","article-title":"T helper subsets in Sjogren\u2019s syndrome and IgG4-related dacryoadenitis and sialoadenitis: A critical review","volume":"51","author":"Moriyama","year":"2014","journal-title":"J. Autoimmun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5527","DOI":"10.4049\/jimmunol.158.11.5527","article-title":"Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II proteins in salivary glands of TGF-\u03b21 knockout mice: MHC class II is a factor in the pathogenesis of TGF-\u03b21 knockout mice","volume":"158","author":"Nakabayashi","year":"1997","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1007\/s10753-011-9356-y","article-title":"Destruction of salivary and lacrimal glands by Th1-polarized reaction in a model of secondary Sjogren\u2019s syndrome in lupus-prone female NZB\u00d7 NZWF1 mice","volume":"35","author":"Hayashi","year":"2012","journal-title":"Inflammation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/j.0300-9475.2004.01508.x","article-title":"A dual role for interferon-\u03b3 in the pathogenesis of Sjogren\u2019s syndrome-like autoimmune exocrinopathy in the nonobese diabetic mouse","volume":"60","author":"Cha","year":"2004","journal-title":"Scand. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/jcla.1860070309","article-title":"Expression of cell adhesion molecules in the salivary and lacrimal glands of Sjogren\u2019s syndrome","volume":"7","author":"Saito","year":"1993","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_56","first-page":"28","article-title":"Regulation of human leukocyte antigen expression in human conjunctival epithelium","volume":"40","author":"Tsubota","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6279","DOI":"10.1167\/iovs.10-7081","article-title":"Interferon-\u03b3 exacerbates dry eye-induced apoptosis in conjunctiva through dual apoptotic pathways","volume":"52","author":"Zhang","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.ajpath.2011.06.030","article-title":"Desiccating Stress Induces CD4+ T-Cell-Mediated Sjogren\u2019s Syndrome-Like Corneal Epithelial Apoptosis via Activation of the Extrinsic Apoptotic Pathway by Interferon-\u03b3","volume":"179","author":"Zhang","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.exer.2013.11.011","article-title":"Topical interferon-\u03b3 neutralization prevents conjunctival goblet cell loss in experimental murine dry eye","volume":"118","author":"Zhang","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/ar3348","article-title":"Disturbance of cytokine networks in Sjogren\u2019s syndrome","volume":"13","author":"Youinou","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1136\/ard.2009.115378","article-title":"Cytokines in Sjogren\u2019s syndrome: Potential therapeutic targets","volume":"69","author":"Roescher","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"39026","DOI":"10.1038\/srep39026","article-title":"Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice","volume":"6","author":"Cho","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/rheumatology\/34.3.226","article-title":"Interferon-\u03b3 and epithelial cell activation in Sjogren\u2019s syndrome","volume":"34","author":"Brookes","year":"1995","journal-title":"Br. J. Rheumatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/icb.2008.70","article-title":"Inflammatory caspases are critical for enhanced cell death in the target tissue of Sjogren\u2019s syndrome before disease onset","volume":"87","author":"Bulosan","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/08916939409014674","article-title":"A model to study viral and cytokine involvement in Sjogren\u2019s syndrome","volume":"18","author":"Clark","year":"1994","journal-title":"Autoimmunity"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1089\/107999000750053771","article-title":"Interferon-mediated block in cell cycle and altered integrin expression in a differentiated salivary gland cell line (HSG) cultured on Matrigel","volume":"20","author":"Daniels","year":"2000","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0889-857X(21)00314-8","article-title":"Pathogenesis of Sjogren\u2019s syndrome","volume":"18","author":"Fox","year":"1992","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1002\/art.38007","article-title":"Interleukin-7 enhances the Th1 response to promote the development of Sjogren\u2019s syndrome-like autoimmune exocrinopathy in mice","volume":"65","author":"Jin","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1002\/art.10577","article-title":"Involvement of the interferon-\u03b3-induced T cell-attracting chemokines, interferon-\u03b3-inducible 10-kd protein (CXCL10) and monokine induced by interferon-\u03b3 (CXCL9), in the salivary gland lesions of patients with Sjogren\u2019s syndrome","volume":"46","author":"Ogawa","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/(SICI)1097-4652(199605)167:2<297::AID-JCP14>3.0.CO;2-5","article-title":"Interferon-\u03b3 induced cell death in a cultured human salivary gland cell line","volume":"167","author":"Wu","year":"1996","journal-title":"J. Cell Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"744","DOI":"10.2353\/ajpath.2010.091116","article-title":"Spontaneous autoimmune dacryoadenitis in aged CD25KO mice","volume":"177","author":"Rahimy","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/MCG.0000000000000410","article-title":"The Long-term Efficacy and Safety of Fecal Microbiota Transplant for Recurrent, Severe, and Complicated Clostridium difficile Infection in 146 Elderly Individuals","volume":"50","author":"Agrawal","year":"2015","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.crohns.2014.08.006","article-title":"Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis","volume":"8","author":"Colman","year":"2014","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/ajg.2014.133","article-title":"Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients","volume":"109","author":"Kelly","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/mi.2009.5","article-title":"IL-17 disrupts corneal barrier following desiccating stress","volume":"2","author":"Chotikavanich","year":"2009","journal-title":"Mucosal Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1167\/iovs.14-15668","article-title":"Age-related conjunctival disease in the C57BL\/6.NOD-Aec1Aec2 Mouse Model of Sjogren Syndrome develops independent of lacrimal dysfunction","volume":"56","author":"You","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nm.2657","article-title":"Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation","volume":"18","author":"Hill","year":"2012","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1002\/jcp.24636","article-title":"Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model","volume":"229","author":"Britton","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40168-015-0106-5","article-title":"Cultivation of stable, reproducible microbial communities from different fecal donors using minibioreactor arrays (MBRAs)","volume":"3","author":"Auchtung","year":"2015","journal-title":"Microbiome"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40168-015-0097-2","article-title":"Humanized microbiota mice as a model of recurrent Clostridium difficile disease","volume":"3","author":"Collins","year":"2015","journal-title":"Microbiome"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1128\/AEM.01541-09","article-title":"Introducing mothur: Open-source, platform-independent, community-supported software for describing and comparing microbial communities","volume":"75","author":"Schloss","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5112","DOI":"10.1128\/AEM.01043-13","article-title":"Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform","volume":"79","author":"Kozich","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"McMurdie, P.J., and Holmes, S. (2013). phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061217"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/2\/565\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:55:00Z","timestamp":1760194500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/2\/565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,13]]},"references-count":83,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2]]}},"alternative-id":["ijms19020565"],"URL":"https:\/\/doi.org\/10.3390\/ijms19020565","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,13]]}}}