{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:24:26Z","timestamp":1786958666470,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Type 1 diabetes (T1D) results from T cell\u2010mediated destruction of insulin\u2010producing pancreatic beta\u2010cells. Recently, the immune\u2010provoking role of stress\u2010related neoantigens has become evident. Neoantigens unlikely contribute to central tolerance and therefore hold strong immunogenic potential, but their role in peripheral immune regulation is unknown. Here, we sought proof of concept that Tregs can be generated against islet neoantigen INS\u2010DRiP that results from stress\u2010induced ribosomal misreads of insulin mRNA. Tregs were induced from na\u00efve CD4 T cells isolated from a healthy donor and co\u2010cultured with monocyte\u2010derived tolerogenic DCs either pulsed with neoantigen INS\u2010DRiP or native autoantigen (proinsulin\u2010peptide C19A3) that can induce Tregs in T1D patients. Their phenotypes, cytokine profiles and suppressive capacity were compared. Tregs induced against neoantigen completely inhibited proliferation of na\u00efve T cells upon cognate antigen\u2010pulsed DC stimulation, which was indistinguishable from Tregs induced against C19A3. Phenotype and cytokine profiling showed co\u2010clustering of native autoantigen\u2010 and neoantigen\u2010specific Tregs, and distinction from T cells generated with antigen\u2010pulsed proinflammatory instead of tolerogenic DCs. Na\u00efve T cells exist against islet neoantigen that can be primed to become Tregs despite the high immunogenic potential of neoantigen. Induction of immune regulation to neoantigens may be useful as immune intervention or prevention of T1D.<\/jats:p>","DOI":"10.1002\/eji.70229","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:18:52Z","timestamp":1782973132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Generation of Regulatory T Cells Against Islet Neoantigen"],"prefix":"10.1002","volume":"56","author":[{"given":"Nicoline H. M.","family":"Den Hollander","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Gootjes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurits G.","family":"Staal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette M.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart O.","family":"Roep","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diahann T. 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