{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:12:21Z","timestamp":1790255541446,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,4]]},"abstract":"<jats:p>\n                    Primary Sj\u00f6gren's Syndrome (pSS) is an autoimmune disease involving salivary and other exocrine glands that leads to progressive lymphocytic infiltration into the gland, tissue damage, and secretory defects. The mechanism underlying this disease remains poorly understood. Here we report that mice with T-cell\u2013targeted deletion of Stromal Interaction Molecule (STIM) 1 and STIM2 [double-knockout (DKO)] mice develop spontaneous and severe pSS-like autoimmune disease, displaying major hallmarks of the disease. In DKO mice, diffuse lymphocytic infiltration was seen in submandibular glands, a major target of pSS, by age 6 wk, progressing to severe inflammation by age 12 wk. Sj\u00f6gren's syndrome-specific autoantibodies (SSA\/Ro and SSB\/La) were detected in the serum, and progressive salivary gland destruction and loss of fluid secretion were also seen. Importantly, we report that peripheral blood mononuclear cells as well as lymphocytic infiltrates in submandibular glands from patients with pSS demonstrated significant reductions in STIM1 and STIM2 proteins. Store-operated calcium entry was also reduced in peripheral blood mononuclear cells from pSS patients compared with those from healthy controls. Thus, deficiency of STIM1 and STIM2 proteins in T cells, and consequent defects in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling, are associated with salivary gland autoimmunopathy in DKO mice and pSS patients. These data reveal a previously unreported link between STIM1 and STIM2 proteins and pSS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1207354109","type":"journal-article","created":{"date-parts":[[2012,8,18]],"date-time":"2012-08-18T01:22:24Z","timestamp":1345252944000},"page":"14544-14549","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":67,"title":["STIM1 and STIM2 protein deficiency in T lymphocytes underlies development of the exocrine gland autoimmune disease, Sj\u00f6gren's syndrome"],"prefix":"10.1073","volume":"109","author":[{"given":"Kwong Tai","family":"Cheng","sequence":"first","affiliation":[{"name":"Secretory Physiology Section,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Alevizos","sequence":"additional","affiliation":[{"name":"Sj\u00f6gren\u2019s Syndrome Clinic, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xibao","family":"Liu","sequence":"additional","affiliation":[{"name":"Secretory Physiology Section,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiliam D.","family":"Swaim","sequence":"additional","affiliation":[{"name":"Secretory Physiology Section,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongen","family":"Yin","sequence":"additional","affiliation":[{"name":"AAV Biology Unit, Molecular Physiology and Therapeutic Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Feske","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Langone Medical Center, New York, NY 10016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatsugu","family":"Oh-hora","sequence":"additional","affiliation":[{"name":"Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases and"},{"name":"Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; 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