Viviane Nascimento Da Conceicao , Yuyang Sun , Xiufang Chai , Julian L. Ambrus , Bibhuti B. Mishra , Brij B. Singh
{"title":"Metformin-induced activation of Ca2+ signaling prevents immune infiltration/pathology in Sjogren’s syndrome-prone mouse models","authors":"Viviane Nascimento Da Conceicao , Yuyang Sun , Xiufang Chai , Julian L. Ambrus , Bibhuti B. Mishra , Brij B. Singh","doi":"10.1016/j.jtauto.2023.100210","DOIUrl":null,"url":null,"abstract":"<div><p>Immune cell infiltration and glandular dysfunction are the hallmarks of autoimmune diseases such as primary Sjogren’s syndrome (pSS), however, the mechanism(s) is unknown. Our data show that metformin-treatment induces <em>Ca2+ signaling that restores saliva secretion and prevents immune cell infiltration in</em> the salivary glands of IL14α-transgenic mice (IL14α), which is a model for pSS. Mechanistically, we show that loss of <em>Ca2+ signaling is a major contributing factor, which is restored by metformin treatment,</em> in IL14α mice. Furthermore, the loss of <em>Ca2+ signaling leads to ER stress in salivary glands.</em> Finally, restoration of metformin-induced <em>Ca2+ signaling</em> inhibited the release of alarmins and prevented the activation of ER stress that was essential for immune cell infiltration. These results suggest that loss of metformin-mediated activation of <em>Ca2+</em> signaling prevents ER stress, which inhibited the release of alarmins that induces immune cell infiltration leading to salivary gland dysfunction observed in pSS.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Translational Autoimmunity","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589909023000230","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Immune cell infiltration and glandular dysfunction are the hallmarks of autoimmune diseases such as primary Sjogren’s syndrome (pSS), however, the mechanism(s) is unknown. Our data show that metformin-treatment induces Ca2+ signaling that restores saliva secretion and prevents immune cell infiltration in the salivary glands of IL14α-transgenic mice (IL14α), which is a model for pSS. Mechanistically, we show that loss of Ca2+ signaling is a major contributing factor, which is restored by metformin treatment, in IL14α mice. Furthermore, the loss of Ca2+ signaling leads to ER stress in salivary glands. Finally, restoration of metformin-induced Ca2+ signaling inhibited the release of alarmins and prevented the activation of ER stress that was essential for immune cell infiltration. These results suggest that loss of metformin-mediated activation of Ca2+ signaling prevents ER stress, which inhibited the release of alarmins that induces immune cell infiltration leading to salivary gland dysfunction observed in pSS.