{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:17:43Z","timestamp":1792451863941,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sj\u00f6gren\u2019s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, leading to impaired glandular secretion. To elucidate the pathogenic mechanisms underlying SS, suitable preclinical animal models are essential. In this study, we developed a humanized murine model that captures key immunopathological features of SS patients, and assessed its therapeutic utility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PBMCs obtained from SS patients were stimulated with anti-CD3 and anti-CD28 antibodies for 15 hours, and 1 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      or 2 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      of these cells were intraperitoneally injected into NOD.Cg-\n                      <jats:italic>Prkdc<\/jats:italic>\n                      <jats:sup>scid<\/jats:sup>\n                      <jats:italic>Il2rg<\/jats:italic>\n                      <jats:sup>tm1Wjl<\/jats:sup>\n                      \/SzJ (NSG) mice. At 5 weeks after cell injection, pathological analysis and immunophenotypic characterization of infiltrating immune cells within the salivary gland tissues were performed. To evaluate the efficacy of metformin, NSG mice transplanted with PBMCs were orally administered metformin daily for 5 weeks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mice injected with PBMCs from SS patients exhibited a significant increase in the frequency of human IL-17-producing T cells in the spleen, accompanied by enhanced infiltration of these pro-inflammatory cells into the salivary glands. Histopathological analysis of salivary glands revealed marked immune cell infiltration and a significant reduction in Aquaporin-5 expression in SS-derived PBMC-injected mice. Notably, these pathological changes were associated with the local recruitment of CXCR3+ Th17 cells. Metformin treatment significantly attenuated salivary gland inflammation, reduced the infiltration of pathogenic T cells, and mitigated molecular-level tissue damage in this humanized SS model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The humanized murine model developed in this study effectively reproduced key cellular and molecular features of SS and provided a useful preclinical platform for investigating early-stage disease mechanisms and evaluating novel therapeutic strategies for SS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1793493","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:08:30Z","timestamp":1779430110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of an improved preclinical humanized mouse platform representing the diverse clinical phenotypes of Sj\u00f6gren\u2019s syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin-Sil","family":"Park","sequence":"first","affiliation":[{"name":"Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Pathology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JeongWon","family":"Choi","sequence":"additional","affiliation":[{"name":"Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Pathology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Medical Sciences, Graduate School of The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Yeon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Pathology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Yeon","family":"Kang","sequence":"additional","affiliation":[{"name":"Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Pathology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Medical Sciences, Graduate School of The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hee","family":"Cho","sequence":"additional","affiliation":[{"name":"Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Pathology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Medical Sciences, Graduate School of The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Beom","family":"Lee","sequence":"additional","affiliation":[{"name":"Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Pathology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Medical Sciences, Graduate School of The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-La","family":"Cho","sequence":"additional","affiliation":[{"name":"Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Pathology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Department of Medical Sciences, Graduate School of The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]},{"name":"Divisions of Rheumatology, Department of Internal Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16047","DOI":"10.1038\/nrdp.2016.47","article-title":"Sjogren syndrome","volume":"2","author":"Brito-Zeron","year":"2016","journal-title":"Nat Rev Dis 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