{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:03:42Z","timestamp":1784527422899,"version":"3.55.0"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE027953"],"award-info":[{"award-number":["DE027953"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sj\u00f6gren's Disease (SjD) is an autoimmune disorder characterized by salivary gland hypofunction and lymphocytic infiltration, yet the contribution of fibrosis to glandular dysfunction remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated the NOD\/ShiLtJ mouse as a model for salivary gland fibrosis and used it to examine the impact of antifibrotic therapy on extracellular matrix (ECM) remodeling. To assess therapeutic potential, we treated NOD\/ShiLtJ female mice with nintedanib, an FDA-approved antifibrotic agent used to treat chronic fibrosing interstitial lung disease. Fibrosis was assessed using single-cell RNA sequencing combined with Picrosirius red staining and AI-assisted digital pathology quantification of collagen I patterning with FibroNest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing revealed that fibroblast populations in the submandibular and sublingual salivary glands of the female NOD\/ShiLtJ mouse exhibited increased levels of ECM genes, including\n                      <jats:italic>Col1a1<\/jats:italic>\n                      ,\n                      <jats:italic>Col1a2<\/jats:italic>\n                      , and\n                      <jats:italic>Col3a1<\/jats:italic>\n                      , relative to control mice. Consistent with these transcriptional changes, Picrosirius Red staining, combined with AI-assisted fibrosis quantification of collagen I patterns, demonstrated significant fibrotic remodeling in the periacinar ECM in submandibular glands of female NOD\/ShiLtJ mice relative to controls. Notably, fibrosis severity strongly correlated with the diabetic phenotype characteristic of this strain, and both periductal and periacinar fibrosis progressed with age. An 8-week nintedanib treatment resulted in modest but measurable reductions across multiple fibrotic indices.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings establish the NOD\/ShiLtJ strain as a model of SjD-associated salivary gland fibrosis and provide proof-of-concept evidence supporting antifibrotic strategies as a potential therapeutic avenue for salivary gland dysfunction in SjD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1779014","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:35:18Z","timestamp":1784525718000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibrotic remodeling in the NOD\/ShiLtJ mouse model of Sj\u00f6gren\u2019s disease: insights from single-cell transcriptomics 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