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The underlying disease mechanisms remain poorly understood, and there are no curative therapies. MyD88-mediated signaling is essential for SjD, although the pathways that rely on MyD88 are not well characterized. Our objective was to determine if MyD88-dependent IL-1 cytokines mediate inflammation in SjD. Using a SjD mouse model and patient samples, RNA sequencing was performed on salivary tissue and peripheral B cells. Splenocytes from SjD mice were stimulated with IL-36 cytokines and B cell activation was assessed. Finally, ELISAs were employed to measure IL-36 in SjD patient sera. Our data revealed that IL-1 family\u2013associated genes were dysregulated in SjD salivary tissue. Salivary B cells showed upregulation of genes associated with MyD88 and IL-36 activation and peripheral B cells from SjD mice had dysregulated IL-1 signaling networks. Moreover, B cells from SjD mice showed enhanced activation when stimulated with IL-36 cytokines, and splenocytes derived from SjD mice exhibited elevated cytokine secretion. Finally, high levels of IL-36\u03b1 and IL-36\u03b3 were present in SjD patient sera and IL-36\u03b1 levels discriminated SjD patients from non-SjD control subjects. Therefore, IL-36 contributes to disease, and drugs targeting IL-1 cytokines, particularly IL-36, may represent novel therapeutic targets for SjD.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf183","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:55:00Z","timestamp":1766148900000},"source":"Crossref","is-referenced-by-count":1,"title":["IL-36 mediates immune activation in Sj\u00f6gren's disease and may represent a novel biomarker of disease"],"prefix":"10.1093","volume":"118","author":[{"given":"Bayan","family":"Alhaddad","sequence":"first","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York , 516 Biomedical Research Building, Buffalo, NY 14214 ,","place":["United States"]},{"name":"Department of Biomedical Science, College of Dentistry, Imam Abdulrahman Bin Faisal University , P.O. Box 1982, Dammam 31441 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Wrynn","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York , 516 Biomedical Research Building, Buffalo, NY 14214 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Kiripolsky","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York , 516 Biomedical Research Building, Buffalo, NY 14214 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M","family":"Kasperek","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York , 516 Biomedical Research Building, Buffalo, NY 14214 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C","family":"Miecznikowski","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health and Health Professions, The University at Buffalo, State University of New York , 723 Kimball Tower, Buffalo, NY 14214 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Perez","sequence":"additional","affiliation":[{"name":"Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health Clinical Center , Building 10 Room 1A01, Bethesda, MD 20895 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Twohig","sequence":"additional","affiliation":[{"name":"Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health Clinical Center , Building 10 Room 1A01, Bethesda, MD 20895 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake M","family":"Warner","sequence":"additional","affiliation":[{"name":"Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health Clinical Center , Building 10 Room 1A01, Bethesda, MD 20895 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose-Anne","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York , 516 Biomedical Research Building, Buffalo, NY 14214 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-8556","authenticated-orcid":false,"given":"Jill M","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, 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