{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:34:29Z","timestamp":1781620469142,"version":"3.54.5"},"reference-count":71,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI-0819529"],"award-info":[{"award-number":["AI-0819529"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE-014344"],"award-info":[{"award-number":["DE-014344"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The C57BL\/6.NOD-Aec1Aec2 mouse is considered a highly appropriate model of Sj\u00f6gren\u2019s Syndrome (SS), a human systemic autoimmune disease characterized primarily as the loss of lacrimal and salivary gland functions. This mouse model, as well as other mouse models of SS, have shown that B lymphocytes are essential for the development and onset of observed clinical manifestations. More recently, studies carried out in the C57BL\/6.IL14\u03b1 transgenic mouse have indicated that the marginal zone B (MZB) cell population is responsible for development of SS disease, reflecting recent observations that MZB cells are present in the salivary glands of SS patients and most likely initiate the subsequent loss of exocrine functions. Although MZB cells are difficult to study in vivo and in vitro, we have carried out an ex vivo investigation that uses temporal global RNA transcriptomic analyses to profile differentially expressed genes known to be associated with cell migration. Results indicate a temporal upregulation of specific chemokine, chemokine receptor, and Rho-GTPase genes in the salivary glands of C57BL\/6.NOD-Aec1Aec2 mice that correlate with the early appearance of periductal lymphocyte infiltrations. Using the power of transcriptomic analyses to better define the genetic profile of lymphocytic emigration into the salivary glands of SS mice, new insights into the underlying mechanisms of SS disease development and onset begin to come into focus, thereby establishing a foundation for further in-depth and novel investigations of the covert and early overt phases of SS disease at the cellular level.<\/jats:p>","DOI":"10.3390\/ijms22137176","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T10:06:34Z","timestamp":1625220394000},"page":"7176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Upregulated Chemokine and Rho-GTPase Genes Define Immune Cell Emigration into Salivary Glands of Sj\u00f6gren\u2019s Syndrome-Susceptible C57BL\/6.NOD-Aec1Aec2 Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Ammon B.","family":"Peck","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 100125, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuong Q.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 100125, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4505-796X","authenticated-orcid":false,"given":"Julian L.","family":"Ambrus","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, SUNY Buffalo School of Medicine, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.clim.2019.04.009","article-title":"Sjogren\u2019s Syndrome: An Update on Disease Pathogenesis, Clinical Manifestations and Treatment","volume":"203","author":"Vivino","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrrheum.2017.198","article-title":"Autoimmunity and Primary Immunodeficiency: Two Sides of the Same Coin?","volume":"14","author":"Schmidt","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.3389\/fimmu.2019.02305","article-title":"The Pathogenic Role of Dysregulated Epigenetic Modifications in Autoimmune Diseases","volume":"10","author":"Wu","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.coi.2019.08.006","article-title":"Shared and Unique Immune Alterations in Pre-Clinical Autoimmunity","volume":"61","author":"Bourn","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.coi.2019.07.001","article-title":"Metabolic Regulation of Pathogenic Autoimmunity: Therapeutic Targeting","volume":"61","author":"Teng","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"ref_6","first-page":"S185","article-title":"Type I Interferon Signature in Sjogren\u2019s Syndrome: Pathophysiological and Clinical Implications","volume":"37","author":"Marketos","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.3389\/fimmu.2018.01512","article-title":"The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases","volume":"9","author":"Yin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1097\/bor.0000174210.78449.6b","article-title":"Familial Autoinflammatory Diseases: Genetics, Pathogenesis and Treatment","volume":"17","author":"Stojanov","year":"2005","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1586\/1744666X.2016.1109449","article-title":"Early Diagnosis of Primary Sjogren\u2019s Syndrome: EULAR-SS Task Force Clinical Recommendations","volume":"12","author":"Theander","year":"2016","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/labinvest.3700487","article-title":"Early Pathogenic Events Associated with Sjogren\u2019s Syndrome (Sjs)-Like Disease of the NOD Mouse Using Microarray Analysis","volume":"86","author":"Killedar","year":"2006","journal-title":"Lab. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1365-3083.2012.02749.x","article-title":"Transcriptome Analysis of the Interferon-Signature Defining the Autoimmune Process of Sjogren\u2019s Syndrome","volume":"76","author":"Peck","year":"2012","journal-title":"Scand. J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R174","DOI":"10.1186\/ar4362","article-title":"Transcriptional Landscapes of Emerging Autoimmunity: Transient Aberrations in the Targeted Tissue\u2019s Extracellular Milieu Precede Immune Responses in Sjogren\u2019s Syndrome","volume":"15","author":"Delaleu","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.2741\/2187","article-title":"Sjogren\u2019s Syndrome (Sjs)-Like Disease of Mice: The Importance of B Lymphocytes and Autoantibodies","volume":"12","author":"Nguyen","year":"2007","journal-title":"Front. Biosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.clim.2017.05.001","article-title":"What Can Sjogren\u2019s Syndrome-Like Disease in Mice Contribute to Human Sjogren\u2019s Syndrome?","volume":"182","author":"Peck","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/1529-0131(199801)41:1<150::AID-ART18>3.0.CO;2-T","article-title":"A Novel NOD-Derived Murine Model of Primary Sjogren\u2019s Syndrome","volume":"41","author":"Robinson","year":"1998","journal-title":"Arthritis Rheum."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1177\/0022034513483315","article-title":"Type I Interferon Receptor Deficiency Prevents Murine Sjogren\u2019s Syndrome","volume":"92","author":"Szczerba","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jaut.2005.11.004","article-title":"Sjogren\u2019s Syndrome in the NOD Mouse Model Is an Interleukin-4 Time-Dependent, Antibody Isotype-Specific Autoimmune Disease","volume":"26","author":"Gao","year":"2006","journal-title":"J. Autoimmun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.molimm.2005.09.003","article-title":"Role of Complement and B Lymphocytes in Sjogren\u2019s Syndrome-Like Autoimmune Exocrinopathy of NOD.B10-H2(B) Mice","volume":"43","author":"Nguyen","year":"2006","journal-title":"Mol. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5676","DOI":"10.4049\/jimmunol.177.8.5676","article-title":"Development of Autoimmunity in IL-14 Alpha-Transgenic Mice","volume":"177","author":"Shen","year":"2006","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.clim.2008.10.006","article-title":"IL-14 Alpha, the Nexus for Primary Sjogren\u2019s Disease in Mice and Humans","volume":"130","author":"Shen","year":"2009","journal-title":"Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6355","DOI":"10.4049\/jimmunol.1001520","article-title":"A Role for Lymphotoxin in Primary Sjogren\u2019s Disease","volume":"185","author":"Shen","year":"2010","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.clim.2016.04.008","article-title":"Central Role for Marginal Zone B Cells in an Animal Model of Sjogren\u2019s Syndrome","volume":"168","author":"Shen","year":"2016","journal-title":"Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nri3383","article-title":"Marginal Zone B Cells: Virtues of Innate-Like Antibody-Producing Lymphocytes","volume":"13","author":"Cerutti","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3389\/fonc.2018.00550","article-title":"The NOTCH Pathway and Its Mutations in Mature B Cell Malignancies","volume":"8","author":"Arruga","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.1071632","article-title":"Integrin-Mediated Long-Term B Cell Retention in the Splenic Marginal Zone","volume":"297","author":"Lu","year":"2002","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.immuni.2008.12.016","article-title":"Lunatic and Manic Fringe Cooperatively Marginal Zone B Cell Precursor Competition for Delta-like 1 in Splenic Endothelial Niches","volume":"30","author":"Tan","year":"2009","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6686","DOI":"10.4049\/jimmunol.169.12.6686","article-title":"Cutting Edge: Selection of B Lymphocyte Subsets Is Regulated by Natural IgM","volume":"169","author":"Baker","year":"2002","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1083\/jcb.201612069","article-title":"Rho GTPase Signaling Complexes in Cell Migration and Invasion","volume":"217","author":"Lawson","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1586\/1744666X.2014.891439","article-title":"B-cell Hyperactivity in Primary Sjogren\u2019s Syndrome","volume":"10","author":"Kroese","year":"2014","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/sji.12520","article-title":"Expression of Toll-Like Receptors in Peripheral Blood Mononuclear Cells of Patients with Primary Sjogren\u2019s Syndrome","volume":"85","author":"Karlsen","year":"2017","journal-title":"Scand. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ambrus, J.L., Suresh, L., and Peck, A. (2016). Multiple Roles for B-Lymphocytes in Sjogren\u2019s Syndrome. J. Clin. Med., 5.","DOI":"10.3390\/jcm5100087"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.3390\/ijms22041919","article-title":"Early Covert Appearance of Marginal Zone B Cells in Sj\u00f6gren\u2019s Syndrome-Susceptible Mice: Initiators of Subsequent Overt Clinical Disease","volume":"22","author":"Ambrus","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3109\/08916930903510872","article-title":"Type I Interferons in Systemic Autoimmunity","volume":"43","author":"Sozzani","year":"2010","journal-title":"Autoimmunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3389\/fimmu.2013.00142","article-title":"The Interferon-Signature of Sj\u00f6gren\u00b4S Signature: How Unique Biomarkers Can Identify Underlying Inflammatory and Immunopathological Mechanisms of Specific Disease","volume":"4","author":"Nguyen","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1182\/blood-2004-02-0514","article-title":"Mastermind Critically Regulates Notch-Mediated Lymphoid Cell Fate Decisions","volume":"104","author":"Maillard","year":"2004","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S1074-7613(03)00111-0","article-title":"Notch2 Is Preferentially Expressed in Mature B Cells and Indispensable for Marginal Zone B Lineage Development","volume":"18","author":"Saito","year":"2003","journal-title":"Immunity"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.coi.2005.04.009","article-title":"Marginal Zone B Cells in Lymphocyte Activation and Regulation","volume":"17","author":"LopesCarvalho","year":"2005","journal-title":"Curr. Opin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/nri2606","article-title":"Rho Family Gtpases and Their Regulators in Lymphocytes","volume":"9","author":"Tybulewicz","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1182\/blood-2007-09-112169","article-title":"Differential Requirement for DOCK2 in Migration of Plasmacytoid Dendritic Cells versus Myeloid Dendritic Cells","volume":"111","author":"Gotoh","year":"2008","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2014.06.005","article-title":"Dock GEFs and Their Therapeutic Potential: Neuroprotection and Axon Regeneration","volume":"43","author":"Namekata","year":"2014","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ejcb.2014.06.003","article-title":"Dock-Family Exchange Factors in Cell Migration and Disease","volume":"93","author":"Gadea","year":"2014","journal-title":"Eur. J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nrm2476","article-title":"Mammalian Rho GTPases: New Insights into Their Functions from In Vivo Studies","volume":"9","author":"Heasman","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"170","DOI":"10.4161\/cam.5.2.14403","article-title":"Dynamics of the Rho-Family Small Gtpases in Actin Regulation and Motility","volume":"5","author":"Spiering","year":"2011","journal-title":"Cell Adh. Migr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/ni1036","article-title":"B Cell Receptor Signal Strength Determines B Cell Fate","volume":"5","author":"Casola","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1146\/annurev.immunol.23.021704.115728","article-title":"Marginal Zone B Cells","volume":"23","author":"Pillai","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7198","DOI":"10.4049\/jimmunol.162.12.7198","article-title":"IgM(High)CD21(High) lymphocytes Enriched in the Splenic Marginal Zone Generate Effector Cells More Rapidly than the Bulk of Follicular B Cells","volume":"162","author":"Oliver","year":"1999","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10875-005-0355-6","article-title":"TLR-9 Activation of Marginal Zone B Cells in Lupus Mice Regulates Immunity through Increased IL-10 Production","volume":"25","author":"Lenert","year":"2005","journal-title":"J. Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7531","DOI":"10.4049\/jimmunol.178.12.7531","article-title":"TLR Stimulation Modifies Blys Receptor Expression in Follicular and Marginal Zone B Cells","volume":"178","author":"Treml","year":"2007","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1146\/annurev.immunol.021908.132607","article-title":"Human Marginal Zone B Cells","volume":"27","author":"Weill","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"803","DOI":"10.4049\/jimmunol.172.2.803","article-title":"Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells","volume":"172","author":"Attanavanich","year":"2004","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/art.23487","article-title":"Regulatory B Lymphocytes in Humans\u2014A Potential Role in Autoimmunity","volume":"58","author":"Jamin","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.0105-2896.2004.0112.x","article-title":"Development and Selection of Marginal Zone B Cells","volume":"197","author":"LopesCarvalho","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/BOR.0b013e3283025ed4","article-title":"The Role of Innate Immunity in Autoimmune Tissue Injury","volume":"20","author":"Allam","year":"2008","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/ni.3731","article-title":"The Multiple Pathways to Autoimmunity","volume":"18","author":"Theofilopoulos","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/CS20160415","article-title":"The Innate Immune System in Human Systemic Lupus Erythematosus","volume":"131","author":"Weidenbusch","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1002\/eji.1830270935","article-title":"Marginal Zone B Cells Exhibit Unique Activation, Proliferative and Immunoglobulin Secretory Responses","volume":"27","author":"Oliver","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.immuni.2018.05.013","article-title":"Innate Lymphoid Cells: Diversity, Plasticity, and Unique Functions in Immunity","volume":"48","author":"Colonna","year":"2018","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/ni.2830","article-title":"Innate Lymphoid Cells Integrate Stromal and Immunological Signals to Enhance Antibody Production by Splenic Marginal Zone B Cells","volume":"15","author":"Magri","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1186\/ar2560","article-title":"Identification of Possible Candidate Genes Regulating Sjogren\u2019s Syndrome-Associated Autoimmunity: A Potential Role for TNFSF4 in Autoimmune Exocrinopathy","volume":"10","author":"Nguyen","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/88756","article-title":"Compensation between Vav-1 and Vav-2 in B cell Development and Antigen Receptor Signaling","volume":"2","author":"Tedford","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"eaai9192","DOI":"10.1126\/scisignal.aai9192","article-title":"Profiling the Origin, Dynamics, and Function of Traction Force in B Cell Activation","volume":"11","author":"Wang","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/j.imbio.2016.07.015","article-title":"Dock10 Regulates CD23 Expression and Sustains B-Cell Lymphopoiesis in Secondary Lymphoid Tissue","volume":"221","author":"Martinez","year":"2016","journal-title":"Immunobiology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.immuni.2004.07.012","article-title":"Differential Requirements for DOCK2 and Phosphoinositide-3-Kinase Gamma during T and B Lymphocyte Homing","volume":"21","author":"NombelaArrieta","year":"2004","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3389\/fimmu.2018.00243","article-title":"The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production","volume":"9","author":"Ushijima","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.3389\/fimmu.2019.02108","article-title":"Flow Cytometric-Based Analysis of Defects in Lymphocyte Differentiation and Function Due to Inborn Errors of Immunity","volume":"10","author":"Ma","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/ni.1820","article-title":"Dock8 Mutations Cripple B Cell Immunological Synapses, Germinal Centers and Long-Lived Antibody Production","volume":"10","author":"Randall","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.exer.2008.10.006","article-title":"Differential Gene Expressions in the Lacrimal Gland During Development and Onset of Keratoconjunctivitis Sicca in Sjogren\u2019s Syndrome (SJS)-Like Disease of the C57BL\/6.NOD-Aec1Aec2 Mouse","volume":"88","author":"Nguyen","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1167\/iovs.11-7652","article-title":"Gene Expression Profiling of Early-Phase Sjogren\u2019s Syndrome in C57BL\/6.NOD-Aec1Aec2 Mice Identifies Focal Adhesion Maturation Associated with Infiltrating Leukocytes","volume":"52","author":"Peck","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","unstructured":"(2021, June 17). The R Project for Statistical Computing. Available online: www.r-project.org."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjanini","year":"1995","journal-title":"J. R Statist. Soc. B"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:25:17Z","timestamp":1760163917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,2]]},"references-count":71,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22137176"],"URL":"https:\/\/doi.org\/10.3390\/ijms22137176","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,2]]}}}