{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:56:05Z","timestamp":1790283365411,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["RGPIN-2024-04744"],"award-info":[{"award-number":["RGPIN-2024-04744"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In type 1 diabetes (T1D) in non-obese diabetic (NOD) mice, dendritic cells (DCs) exhibit a Stat5b mutation that impairs regulatory T cell (Tregs) numbers and suppressive function. To correct this defect, we generated transgenic NOD mice expressing constitutively active Stat5b (NOD.Stat5b-CA) in DCs, which conferred protection from diabetes that was associated with an expanded Treg population and a marked reduction in CD8+ T cell frequencies in secondary lymphoid organs. However, the phenotypic characteristics and underlying mechanisms to eliminate CD8+ T cells in NOD.Stat5b-CA mice are unknown. In this study, we found that the frequency of Tregs was significantly higher in the thymus and peripheral lymphoid organs of NOD.Stat5b-CA mice compared with NOD mice. Tregs in the peripheral lymphoid organs exhibited increased expression of activation markers CD69 and OX40, alongside reduced CD62L. We also found that CD8+ T cell frequencies were reduced in the peripheral organs but not in the thymus of NOD.Stat5b-CA mice, while CD4+ T cell frequencies remained unchanged across all organs. Furthermore, NOD.Stat5b-CA mice exhibited a reduced frequency of central Tregs (CD62Lhigh CD44low) and increased frequency of effector Tregs (CD62Llow CD44high) under steady-state conditions compared to NOD mice. Notably, Tregs from NOD.Stat5b-CA mice displayed enhanced cytotoxic activity, evidenced by increased expression of perforin, granzyme B, and Fas ligand, potentially mediating CD8+ T cell frequency reduction. Collectively, these findings highlight a novel role for Stat5b-CA.DC-educated Tregs in modulating immune responses by eliminating peripheral pathogenic CD8+ T cells via cytotoxic pathways, thereby contributing to immune regulation in NOD.Stat5b-CA mice.<\/jats:p>","DOI":"10.3390\/ijms27020794","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:40:09Z","timestamp":1768329609000},"page":"794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Constitutively Active Stat5b Expression in Dendritic Cells Enhances Treg-Mediated Elimination of Autoreactive CD8+ T Cells in Autoimmune Diabetes"],"prefix":"10.3390","volume":"27","author":[{"given":"Puregmaa","family":"Khongorzul","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Centre de Recherche du CHUS, Universit\u00e9 de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhan Ullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Centre de Recherche du CHUS, Universit\u00e9 de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphn\u00e9e","family":"Levasseur","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Centre de Recherche du CHUS, Universit\u00e9 de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1215-2434","authenticated-orcid":false,"given":"Denis","family":"Gris","sequence":"additional","affiliation":[{"name":"Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Centre de Recherche du CHUS, Universit\u00e9 de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelaziz","family":"Amrani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Centre de Recherche du CHUS, Universit\u00e9 de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grover, P., Goel, P.N., and Greene, M.I. 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