{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:34:10Z","timestamp":1792056850299,"version":"4.4.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary Sj\u00f6gren\u2019s syndrome (pSS) is a complex autoimmune disease starting in the salivary and lacrimal glands and continuing to involve the lungs and kidneys with the eventual development of lymphoma. Many studies have emphasized the role of type 1 IFN (IFN-\u03b1) and lymphotoxin \u03b1 (LT\u03b1) in the pathogenesis of the disease. The present studies were designed to delineate the role of IFN-\u03b1 in pSS using an animal model, the IL-14\u03b1 (IL14\u03b1TG) transgenic mouse. IL14\u03b1TG mice lacking the type 1 IFNR (IL14\u03b1TG.IFNR\u2212\/\u2212) had the same submandibular gland and lacrimal gland injury as did the IL14\u03b1TG mice, but they lacked the later parotid gland and lung injury. Development of lymphoma was delayed in IL14\u03b1TG.IFNR\u2212\/\u2212 mice. The switch from IgM to IgG autoantibodies as well as the increase in serum IgG2a seen is IL14\u03b1TG mice was inhibited in IL14\u03b1TG.IFNR\u2212\/\u2212 mice. Production of LT\u03b1 was identified in both IL14\u03b1TG mice and IL14\u03b1TG.IFNR\u2212\/\u2212 mice at the time that salivary gland injury was occurring. These and previous studies suggest a model for pSS that separates the disease into several stages: 1) initial injury to the submandibular and lacrimal glands via an environmental insult and LT\u03b1; 2) amplification of local injury via the production of type 1 IFN; injury to the parotid glands, lungs, and kidneys is seen; 3) progression of systemic inflammation with the eventual development of large B cell lymphoma. Understanding these different stages will help to develop strategies for treatment of patients with pSS based on the status of their disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1203440","type":"journal-article","created":{"date-parts":[[2013,6,15]],"date-time":"2013-06-15T04:10:33Z","timestamp":1371269433000},"page":"608-613","source":"Crossref","is-referenced-by-count":44,"title":["Different Stages of Primary Sj\u00f6gren\u2019s Syndrome Involving Lymphotoxin and Type 1 IFN"],"prefix":"10.1093","volume":"191","author":[{"given":"Long","family":"Shen","sequence":"first","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmanan","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnostics Sciences, State University of New York at Buffalo School of Dental Medicine , Buffalo, NY 14214"},{"name":"IMMCO Diagnostics, Inc. , Buffalo, NY 14228"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishore","family":"Malyavantham","sequence":"additional","affiliation":[{"name":"IMMCO Diagnostics, Inc. , Buffalo, NY 14228"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemek","family":"Kowal","sequence":"additional","affiliation":[{"name":"IMMCO Diagnostics, Inc. , Buffalo, NY 14228"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxiu","family":"Xuan","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Lindemann","sequence":"additional","affiliation":[{"name":"IMMCO Diagnostics, Inc. , Buffalo, NY 14228"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Julian L","family":"Ambrus","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"2025032405083673100_r1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0049-0172(84)90001-5","article-title":"Primary Sjogren syndrome: clinical and immunopathologic features","volume":"14","author":"Fox","year":"1984","journal-title":"Semin. Arthritis Rheum."},{"issue":"5","key":"2025032405083673100_r2","first-page":"S66","article-title":"Mortality in Sj\u00f6gren\u2019s syndrome","volume":"26","author":"Voulgarelis","year":"2008","journal-title":"Clin. Exp. Rheumatol."},{"key":"2025032405083673100_r3","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1073\/pnas.0510837103","article-title":"Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sj\u00f6gren\u2019s syndrome","volume":"103","author":"Gottenberg","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032405083673100_r4","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/BOR.0b013e32832eba21","article-title":"Pathogenesis of Sj\u00f6gren\u2019s syndrome","volume":"21","author":"Nikolov","year":"2009","journal-title":"Curr. Opin. Rheumatol."},{"key":"2025032405083673100_r5","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.immuni.2006.08.010","article-title":"Type I interferon in systemic lupus erythematosus and other autoimmune diseases","volume":"25","author":"Banchereau","year":"2006","journal-title":"Immunity"},{"key":"2025032405083673100_r6","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1601-0825.2007.01376.x","article-title":"Usefulness of mouse models to study the pathogenesis of Sj\u00f6gren\u2019s syndrome","volume":"13","author":"Soyfoo","year":"2007","journal-title":"Oral Dis."},{"key":"2025032405083673100_r7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12016-011-8288-5","article-title":"Animal models in autoimmune diseases: lessons learned from mouse models for Sj\u00f6gren\u2019s syndrome","volume":"42","author":"Lee","year":"2012","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"2025032405083673100_r8","doi-asserted-by":"crossref","first-page":"5676","DOI":"10.4049\/jimmunol.177.8.5676","article-title":"Development of autoimmunity in IL-14\u03b1-transgenic mice","volume":"177","author":"Shen","year":"2006","journal-title":"J. Immunol."},{"key":"2025032405083673100_r9","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.clim.2008.10.006","article-title":"IL-14\u03b1, the nexus for primary Sj\u00f6gren\u2019s disease in mice and humans","volume":"130","author":"Shen","year":"2009","journal-title":"Clin. Immunol."},{"key":"2025032405083673100_r10","doi-asserted-by":"crossref","first-page":"6355","DOI":"10.4049\/jimmunol.1001520","article-title":"A role for lymphotoxin in primary Sj\u00f6gren\u2019s disease","volume":"185","author":"Shen","year":"2010","journal-title":"J. Immunol."},{"key":"2025032405083673100_r11","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.clim.2012.09.013","article-title":"Novel autoantibodies in Sjogren\u2019s syndrome","volume":"145","author":"Shen","year":"2012","journal-title":"Clin. Immunol."},{"key":"2025032405083673100_r12","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1126\/science.8009221","article-title":"Functional role of type I and type II interferons in antiviral defense","volume":"264","author":"M\u00fcller","year":"1994","journal-title":"Science"},{"key":"2025032405083673100_r13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1136\/ard.2006.052647","article-title":"Progression of salivary gland dysfunction in patients with Sj\u00f6gren\u2019s syndrome","volume":"66","author":"Pijpe","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"2025032405083673100_r14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jaut.2012.03.001","article-title":"Subgroups of Sj\u00f6gren syndrome patients according to serological profiles","volume":"39","author":"Bournia","year":"2012","journal-title":"J. Autoimmun."},{"key":"2025032405083673100_r15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.autrev.2010.09.001","article-title":"The meaning of anti-Ro and anti-La antibodies in primary Sj\u00f6gren\u2019s syndrome","volume":"10","author":"Hern\u00e1ndez-Molina","year":"2011","journal-title":"Autoimmun. Rev."},{"key":"2025032405083673100_r16","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1084\/jem.174.5.1179","article-title":"Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice","volume":"174","author":"Finkelman","year":"1991","journal-title":"J. Exp. Med."},{"key":"2025032405083673100_r17","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1136\/ard.2008.095257","article-title":"Quantitative assessment of antibodies to ribonucleoproteins in primary Sj\u00f6gren syndrome: correlation with B-cell biomarkers and disease activity","volume":"68","author":"Candon","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"2025032405083673100_r18","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/ncprheum0173","article-title":"Mechanisms of disease: primary Sj\u00f6gren\u2019s syndrome and the type I interferon system","volume":"2","author":"Nordmark","year":"2006","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"2025032405083673100_r19","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.4049\/jimmunol.1003208","article-title":"IFN-\u03b1 directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity","volume":"186","author":"Terawaki","year":"2011","journal-title":"J. Immunol."},{"key":"2025032405083673100_r20","first-page":"367","article-title":"Interferon \u03b1-2 (IFN\u03b12) increases lacrimal and salivary function in Sj\u00f6gren\u2019s syndrome patients. Preliminary results of an open pilot trial versus OH-chloroquine","volume":"14","author":"Ferraccioli","year":"1996","journal-title":"Clin. Exp. Rheumatol."},{"key":"2025032405083673100_r21","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1136\/ard.2009.115378","article-title":"Cytokines in Sj\u00f6gren\u2019s syndrome: potential therapeutic targets","volume":"69","author":"Roescher","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"2025032405083673100_r22","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1089\/107999099313497","article-title":"Treatment of primary Sj\u00f6gren\u2019s syndrome with low-dose natural human interferon-\u03b1 administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group","volume":"19","author":"Ship","year":"1999","journal-title":"J. Interferon Cytokine Res."},{"key":"2025032405083673100_r23","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1002\/eji.1830271026","article-title":"Human recombinant interferon-\u03b2 influences T helper subset differentiation by regulating cytokine secretion pattern and expression of homing receptors","volume":"27","author":"McRae","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"2025032405083673100_r24","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1385\/IR:34:3:243","article-title":"Restoring immune defenses via lymphotoxin signaling: lessons from cytomegalovirus","volume":"34","author":"Banks","year":"2006","journal-title":"Immunol. Res."},{"key":"2025032405083673100_r25","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/10428190902780677","article-title":"Autoimmunity and hematologic malignancies: associations and mechanisms","volume":"50","author":"Martin","year":"2009","journal-title":"Leuk. Lymphoma"},{"key":"2025032405083673100_r26","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1136\/ard.2005.041186","article-title":"Lymphoma and other malignancies in primary Sj\u00f6gren\u2019s syndrome: a cohort study on cancer incidence and lymphoma predictors","volume":"65","author":"Theander","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"2025032405083673100_r27","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.4049\/jimmunol.137.10.3153","article-title":"Effect of interferon-alpha on immunoglobulin synthesis by human B cells","volume":"137","author":"Peters","year":"1986","journal-title":"J. Immunol."},{"key":"2025032405083673100_r28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1089\/107999099314009","article-title":"Human type I interferons differ greatly in their effects on the proliferation of primary B cells","volume":"19","author":"Hibbert","year":"1999","journal-title":"J. Interferon Cytokine Res."},{"key":"2025032405083673100_r29","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/gene.2009.20","article-title":"Peripheral blood gene expression profiling in Sj\u00f6gren\u2019s syndrome","volume":"10","author":"Emamian","year":"2009","journal-title":"Genes Immun."},{"key":"2025032405083673100_r30","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.4049\/jimmunol.181.3.2211","article-title":"Excessive production of IFN-\u03b3 in patients with systemic lupus erythematosus and its contribution to induction of B lymphocyte stimulator\/B cell-activating factor\/TNF ligand superfamily-13B","volume":"181","author":"Harigai","year":"2008","journal-title":"J. Immunol."},{"key":"2025032405083673100_r31","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1002\/art.24557","article-title":"Neutralization of interferon-\u03b1\/\u03b2-inducible genes and downstream effect in a phase I trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus","volume":"60","author":"Yao","year":"2009","journal-title":"Arthritis Rheum."},{"key":"2025032405083673100_r32","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/art.22603","article-title":"BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sj\u00f6gren\u2019s syndrome","volume":"56","author":"Pers","year":"2007","journal-title":"Arthritis Rheum."},{"key":"2025032405083673100_r33","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1002\/art.22458","article-title":"Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sj\u00f6gren\u2019s syndrome","volume":"56","author":"Daridon","year":"2007","journal-title":"Arthritis Rheum."},{"key":"2025032405083673100_r34","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1365-3083.2007.02049.x","article-title":"B-cell activating factor of the tumour necrosis factor family expression in blood monocytes and T cells from patients with primary Sj\u00f6gren\u2019s syndrome","volume":"67","author":"Lavie","year":"2008","journal-title":"Scand. J. Immunol."},{"key":"2025032405083673100_r35","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1172\/JCI113235","article-title":"Expression of Bcl-2 and Bcl-2-Ig fusion transcripts in normal and neoplastic cells","volume":"80","author":"Graninger","year":"1987","journal-title":"J. Clin. Invest."},{"key":"2025032405083673100_r36","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1182\/blood-2006-08-038497","article-title":"Development of a murine model for blastoid variant mantle-cell lymphoma","volume":"109","author":"Ford","year":"2007","journal-title":"Blood"},{"key":"2025032405083673100_r37","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1084\/jem.20051283","article-title":"BAFF regulates B cell survival by downregulating the BH3-only family member Bim via the ERK pathway","volume":"202","author":"Craxton","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032405083673100_r38","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1002\/eji.200636270","article-title":"Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone B cells","volume":"36","author":"Fletcher","year":"2006","journal-title":"Eur. J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/2\/608\/62507768\/1203440.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/2\/608\/62507768\/1203440.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T22:42:04Z","timestamp":1742856124000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/191\/2\/608\/7991129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,7,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1203440","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,7]]},"published":{"date-parts":[[2013,7]]}}}