{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:13:56Z","timestamp":1789715636468,"version":"4.0.1"},"reference-count":57,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE014756"],"award-info":[{"award-number":["DE014756"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The molecular mechanisms leading to saliva secretion are largely established, but factors that underlie secretory hypofunction, specifically related to the autoimmune disease Sj\u00f6gren\u2019s syndrome (SS) are not fully understood. A major conundrum is the lack of association between the severity of salivary gland immune cell infiltration and glandular hypofunction. SS-like disease was induced by treatment with DMXAA, a small molecule agonist of murine STING. We have previously shown that the extent of salivary secretion is correlated with the magnitude of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals (Takano et al., 2021). Contrary to our expectations, despite a significant reduction in fluid secretion, neural stimulation resulted in enhanced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals with altered spatiotemporal characteristics in vivo. Muscarinic stimulation resulted in reduced activation of the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated Cl\n                    <jats:sup>-<\/jats:sup>\n                    channel, TMEM16a, although there were no changes in channel abundance or absolute sensitivity to Ca\n                    <jats:sup>2+<\/jats:sup>\n                    . Super-resolution microscopy revealed a disruption in the colocalization of Inositol 1,4,5-trisphosphate receptor Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release channels with TMEM16a, and channel activation was reduced when intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    buffering was increased. These data indicate altered local peripheral coupling between the channels. Appropriate Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling is also pivotal for mitochondrial morphology and bioenergetics. Disrupted mitochondrial morphology and reduced oxygen consumption rate were observed in DMXAA-treated animals. In summary, early in SS disease, dysregulated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals lead to decreased fluid secretion and disrupted mitochondrial function contributing to salivary gland hypofunction.\n                  <\/jats:p>","DOI":"10.7554\/elife.97069","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T11:25:16Z","timestamp":1716549916000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.97069","source":"Crossref","is-referenced-by-count":15,"title":["Dysregulated Ca2+ signaling, fluid secretion, and mitochondrial function in a mouse model of early Sj\u00f6gren\u2019s disease"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3138-3406","authenticated-orcid":true,"given":"Kai-Ting","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022kthw22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology and Physiology, University of Rochester","place":["Rochester, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-8697","authenticated-orcid":true,"given":"Larry E","family":"Wagner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022kthw22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology and Physiology, University of Rochester","place":["Rochester, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Takahiro","family":"Takano","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022kthw22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology and Physiology, University of Rochester","place":["Rochester, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xiao-Xuan","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022kthw22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology and Physiology, University of Rochester","place":["Rochester, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Harini","family":"Bagavant","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035z6xf33","id-type":"ROR","asserted-by":"publisher"}],"name":"Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation","place":["Oklahoma City, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Umesh","family":"Deshmukh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035z6xf33","id-type":"ROR","asserted-by":"publisher"}],"name":"Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation","place":["Oklahoma City, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6743-0668","authenticated-orcid":true,"given":"David I","family":"Yule","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022kthw22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology and Physiology, University of Rochester","place":["Rochester, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1002\/cpim.114","type":"journal-article","article-title":"Protocols for experimental sj\u00f6gren\u2019s syndrome","volume":"131","author":"Bagavant","year":"2020","journal-title":"Current Protocols in Immunology"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102867","type":"journal-article","article-title":"Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sj\u00f6gren\u2019s syndrome","volume":"20","author":"Barrera","year":"2021","journal-title":"Autoimmunity Reviews"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.47","type":"journal-article","article-title":"Sj\u00f6gren syndrome","volume":"2","author":"Brito-Zer\u00f3n","year":"2016","journal-title":"Nature Reviews. 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