{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:50:32Z","timestamp":1790211032311,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Salivary gland epithelial cells (SGECs) are key cellular drivers in the pathogenesis of primary Sj\u00f6gren's syndrome (SS); however, the mechanisms sustaining SGEC activation in primary SS remain unclear. We undertook this study to determine the role of autophagy in the survival and activation of SGECs in primary SS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary SGECs isolated from the minor SGs of patients with primary SS or sicca syndrome were evaluated by flow cytometry, immunoblotting, and immunofluorescence to assess autophagy (autophagic flux, light chain 3 IIB [LC3\u2010IIB], p62, LC3\u2010IIB+\/lysosome\u2010associated membrane protein 1 [LAMP\u20101] staining), apoptosis (annexin V\/propidium iodide [PI], caspase 3), and activation (intercellular adhesion molecule, vascular cell adhesion molecule). Focus score and germinal center presence were assessed in the SGs from the same patients to assess correlation with histologic severity. Human SG (HSG) cells were stimulated in vitro with peripheral blood mononuclear cells (PBMCs) and serum from primary SS patients in the presence or absence of autophagy inhibitors to determine changes in autophagy and epithelial cell activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SGECs from primary SS patients (n\u00a0=\u00a024) exhibited increased autophagy (autophagic flux [<jats:italic>P<\/jats:italic>\u00a0=\u00a00.001]; LC3\u2010IIB [<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02]; p62 [<jats:italic>P<\/jats:italic>\u00a0=\u00a00.064]; and as indicated by LC3\u2010IIB\/LAMP\u20101+ staining), increased expression of antiapoptotic molecules (Bcl\u20102 [<jats:italic>P<\/jats:italic>\u00a0=\u00a00.006]), and reduced apoptosis (annexin V\/PI [<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002]; caspase 3 [<jats:italic>P<\/jats:italic>\u00a0=\u00a00.057]), compared to samples from patients with sicca syndrome (n\u00a0=\u00a016). Autophagy correlated with histologic disease severity. In vitro experiments on HSG cells stimulated with serum and PBMCs from primary SS patients confirmed activation of autophagy and expression of adhesion molecules, which was reverted upon pharmacologic inhibition of autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In primary SS SGECs, inflammation induces autophagy and prosurvival mechanisms, which promote SGEC activation and mirror histologic severity. These findings indicate that autophagy is a central contributor to the pathogenesis of primary SS and a new therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42018","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T09:38:26Z","timestamp":1636364306000},"page":"654-664","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Maladaptive Autophagy in the Pathogenesis of Autoimmune Epithelitis in Sj\u00f6gren's Syndrome"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7802-1192","authenticated-orcid":false,"given":"Serena","family":"Colafrancesco","sequence":"first","affiliation":[{"name":"Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Barbati","sequence":"additional","affiliation":[{"name":"Sapienza University  Rome 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