{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:03:10Z","timestamp":1789700590216,"version":"4.0.1"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Type 1 diabetes (T1D) results from immune-mediated destruction of pancreatic beta cells. B cells serve as critical antigen-presenting cells whose autoreactive specificities drive disease progression. Conversely, IL-10 producing regulatory B cells (Bregs) exert immunosuppressive functions and have been shown to protect against autoimmunity in mouse models of rheumatoid arthritis and multiple sclerosis, where microenvironmental cues promote their differentiation. In particular, signaling through hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) induces glycolytic flux that supports Breg expansion. Defects in Breg development and function have been identified in both human T1D and the non-obese diabetic (NOD) mouse, but whether these impairments reflect intrinsic B-cell abnormalities or microenvironmental changes associated with hyperglycemia and inflammation remains unclear. Moreover, the mechanisms by which B cells suppress pathogenic T-cell responses likely vary across disease states. Here, we examine how B cell differentiation, metabolism, and HIF-1\u03b1 signaling interact to shape immune regulation in autoimmune diabetes. We show that B cells undergo dynamic metabolic remodeling during disease progression. B cells from NOD mice are characterized by exaggerated glucose uptake and elevated IL-10 expression compared with non-autoimmune B6 B cells, despite reduced HIF-1\u03b1 levels and attenuated induction of HIF-dependent glycolytic genes. These findings indicate that HIF-1\u03b1 plays a diminished role in controlling IL-10 production in NOD B cells and that IL-10 alone is insufficient to maintain immune tolerance. Together, our results highlight how genetic and microenvironmental factors reprogram B cell metabolism and underscore the need to explore IL-10 independent pathways and B-cell extrinsic mechanisms when developing immunomodulatory therapies for T1D.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf330","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T15:35:33Z","timestamp":1766849733000},"source":"Crossref","is-referenced-by-count":2,"title":["Altered B cell metabolic pathways characterize type 1 diabetes progression"],"prefix":"10.1093","volume":"215","author":[{"given":"Holly","family":"Conway","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]},{"name":"Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, IN,","place":["United 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IN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-8663","authenticated-orcid":false,"given":"Carmella","family":"Evans-Molina","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]},{"name":"Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]},{"name":"Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6170-1156","authenticated-orcid":false,"given":"Jamie L","family":"Felton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology, 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