{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:16Z","timestamp":1760060656059,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AR053483","AI082714","GM104938","AR060804","DE028001","J ZK 011-2\/2019-2020"],"award-info":[{"award-number":["AR053483","AI082714","GM104938","AR060804","DE028001","J ZK 011-2\/2019-2020"]}]},{"name":"Onassis Foundation\u2014Scholarship","award":["AR053483","AI082714","GM104938","AR060804","DE028001","J ZK 011-2\/2019-2020"],"award-info":[{"award-number":["AR053483","AI082714","GM104938","AR060804","DE028001","J ZK 011-2\/2019-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sj\u00f6gren\u2019s disease (SjD) targets the salivary and lacrimal glands and is characterized by autoantibody production and glandular lymphocytic infiltrate with ectopic germinal centers (EGCs). The chemokine CCL25 recruits CCR9+ CD4+ T cells to the salivary glands to promote B cell activation. However, the therapeutic potential of targeting the CCL25\u2013CCR9 axis to limit glandular inflammation and lymphoid neogenesis remains largely unexplored. Evaluate whether blocking the CCL25\u2013CCR9+ T cell axis with a monoclonal antibody could reduce immune infiltration, ectopic germinal center (EGC) formation, and local autoantibody production in the NOD.H2(h4) mouse model of SjD. Female NOD.H2(h4) mice were administered anti-CCL25 antibody, isotype control, or PBS intraperitoneally for 12 weeks. Sera and saliva were collected to evaluate anti-Ro52 antibodies via ELISA across treatment groups. Salivary glands were harvested and processed for H&amp;E staining to assess lymphocytic infiltration and focus scores. Treatment with \u03b1-CCL25 was well tolerated, with no significant differences in body weight or stimulated salivary flow between treatment groups. Histopathological evaluation revealed no reduction in lymphocytic infiltration, focus scores, or percentage of inflamed tissue in \u03b1-CCL25-treated mice compared to controls. Anti-Ro52 antibodies were undetectable in plasma or saliva across all groups and timepoints. Systemic CCL25 blockade did not significantly alter salivary gland inflammation, function, or autoantibody production in NOD.H2(h4) mice. These findings suggest that monotherapy targeting the CCL25\u2013CCR9 axis may be insufficient to resolve glandular autoimmunity in this model and that additional or combinatorial strategies may be necessary for effective intervention.<\/jats:p>","DOI":"10.3390\/ijms26188802","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating Anti-CCL25 as a Therapeutic Strategy to Disrupt Foci Formation in a Spontaneous Murine Model of Sj\u00f6gren\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Martha","family":"Tsaliki","sequence":"first","affiliation":[{"name":"Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA"},{"name":"Department of Pathology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA"},{"name":"Department of Veterans Affairs Medical Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-6859","authenticated-orcid":false,"given":"Biji T.","family":"Kurien","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA"},{"name":"Department of Veterans Affairs Medical Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Cavett","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA"},{"name":"Department of Veterans Affairs Medical Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Ice","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA"},{"name":"Department of Veterans Affairs Medical Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristi A.","family":"Koelsch","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA"},{"name":"Department of Pathology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA"},{"name":"Department of Veterans Affairs Medical Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-5850","authenticated-orcid":false,"given":"Robert Hal","family":"Scofield","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA"},{"name":"Department of Pathology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA"},{"name":"Department of Veterans Affairs Medical Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA"},{"name":"Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s10238-021-00728-6","article-title":"Sjogren\u2019s syndrome: A systemic autoimmune disease","volume":"22","author":"Negrini","year":"2022","journal-title":"Clin. Exp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Brandt, J.E., Priori, R., Valesini, G., and Fairweather, D. (2015). Sex differences in Sjogren\u2019s syndrome: A comprehensive review of immune mechanisms. Biol. 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