{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:14:38Z","timestamp":1779138878814,"version":"3.51.4"},"reference-count":86,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-191999"],"award-info":[{"award-number":["PJT-191999"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sanofi","award":["8848"],"award-info":[{"award-number":["8848"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,20]]},"abstract":"<jats:p>\n                    Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR\u2019336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor \u03b1 chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR\u2019336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells\u2019 proliferation and function. Using a murine model of spontaneous type 1 diabetes, we showed that the administration of SAR\u2019336 slows the development of disease in mice by decreasing the degree of insulitis through the expansion of antigen-specific Tregs over Th1 cells in pancreatic islets. Specifically, SAR\u2019336 promoted the differentiation of IL-33\u2013responsive (ST2\n                    <jats:sup>+<\/jats:sup>\n                    ), IL-10\u2013producing GATA3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs over other Treg subsets in the pancreas, demonstrating the ability of this molecule to further orchestrate Treg adaptation. These results offer insight into the capacity of SAR\u2019336 to generate highly specialized, tissue-localized Tregs that promote restoration of homeostasis during ongoing autoimmune disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.182064","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T14:00:32Z","timestamp":1734616832000},"source":"Crossref","is-referenced-by-count":4,"title":["The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes"],"prefix":"10.1172","volume":"9","author":[{"given":"Fernando","family":"Alvarez","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada."},{"name":"Program in Infectious Diseases and Immunology in Global Health, the Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Quebec, Canada."},{"name":"Centre of Excellence in Translational Immunology 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