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However, there are no studies addressing STIM1\/2 dysfunction in salivary glands or SjD in animal models. We report that mice lacking Stim1 and Stim2 [Stim1\/2K14Cre(+)] in salivary glands exhibited reduced Ca2+ levels and hyposalivate. SOCE was functionally required for the activation of the Ca2+ activated Cl\u2212 channel ANO1. Ageing Stim1\/2K14Cre(+) mice showed no evidence of lymphocytic infiltration or increased levels of autoantibodies characteristic of SjD, possibly associated with a downregulation of toll-like receptor 8 (Tlr8) expression. Salivary gland biopsies of SjD patients showed increased expression of STIM1 and TLR7\/8. Our study shows that SOCE activates ANO1 function and fluid secretion in salivary glands and highlights a potential link between SOCE and TLR signaling in SjD.<\/jats:p>","DOI":"10.1093\/function\/zqae047","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T16:17:28Z","timestamp":1730132248000},"source":"Crossref","is-referenced-by-count":6,"title":["Loss of STIM1 and STIM2 in Salivary Glands Disrupts ANO1 Function but Does Not Induce Sjogren\u2019s Disease"],"prefix":"10.1152","volume":"6","author":[{"given":"Ga-Yeon","family":"Son","sequence":"first","affiliation":[{"name":"Department of Molecular Pathobiology, New York University College of Dentistry , New York 10010 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, New York University College of Dentistry , New York 10010 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Wahl","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester , Rochester, New York 14642 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester , Rochester, New York 14642 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saruul","family":"Zorgit","sequence":"additional","affiliation":[{"name":"Biology Program, Division of Science and Mathematics, New York University Abu Dhabi , Abu Dhabi 129188 ,","place":["United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manikandan","family":"Vinu","sequence":"additional","affiliation":[{"name":"Biology Program, Division of Science and Mathematics, New York University Abu Dhabi , Abu Dhabi 129188 ,","place":["United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine , New York, New York 10010 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester , Rochester, New York 14642 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef","family":"Idaghdour","sequence":"additional","affiliation":[{"name":"Biology Program, Division of Science and Mathematics, New York University Abu Dhabi , Abu Dhabi 129188 ,","place":["United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I","family":"Yule","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester , Rochester, New York 14642 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Feske","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine , New York, New York 10010 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo S","family":"Lacruz","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, New York University College of Dentistry , New York 10010 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"issue":"5","key":"2025030421390892900_bib1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41584-023-00932-6","article-title":"Genetics and epigenetics of primary Sjogren syndrome: implications for future therapies","volume":"19","author":"Thorlacius","year":"2023","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"2025030421390892900_bib2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrrheum.2018.1","article-title":"B cells in the pathogenesis of primary Sjogren syndrome","volume":"14","author":"Nocturne","year":"2018","journal-title":"Nat Rev Rheumatol"},{"issue":"11","key":"2025030421390892900_bib3","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1136\/annrheumdis-2014-205375","article-title":"Epidemiology of primary Sjogren's syndrome: a systematic review and meta-analysis","volume":"74","author":"Qin","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"2025030421390892900_bib4","doi-asserted-by":"crossref","first-page":"958670","DOI":"10.3389\/fmed.2022.958670","article-title":"Sex differences in comorbidities associated with Sjogren\u2019s disease","volume":"9","author":"Bruno","year":"2022","journal-title":"Front. 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