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Alliance"],"accepted":{"date-parts":[[2025,9,19]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    The Lnk\/Sh2b3 adaptor protein functions as a regulatory molecule for cytokine signaling in lymphohematopoiesis. A missense variant of the\n                    <jats:italic>LNK\/SH2B3<\/jats:italic>\n                    gene is reportedly a risk variant common to several autoimmune diseases, including type 1 diabetes (T1D). However, roles of Lnk in T1D development remain elusive. We found that\n                    <jats:italic>Lnk<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice showed increased susceptibility to diabetes following treatment with fairly low doses of streptozotocin, manifested by hyperglycemia and insulitis accompanied by accumulation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells and loss of pancreatic \u03b2 cells. The high susceptibility of\n                    <jats:italic>Lnk<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice to islet damage was abolished in crosses with\n                    <jats:italic>Rag2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice lacking lymphocytes or\n                    <jats:italic>MyD88<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice carrying various defects in activation of innate immune cells. In\n                    <jats:italic>Lnk<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice pancreata, dendritic cell (DC) fractions were altered and showed augmented expression of CD40 and IL-27. Treatment with anti-CD40L or anti-GM-CSF antibodies suppressed \u03b2 cell damage and prevented diabetes. Thus, Lnk regulates T-cell priming and expansion via GM-CSF- and possibly IL-27-dependent activation of pancreatic DCs after islet damage.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202503332","type":"journal-article","created":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T06:21:38Z","timestamp":1758349298000},"page":"e202503332","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Lnk\/Sh2b3 regulates initiation and severity of autoimmune insulitis and contributes to diabetes risk"],"prefix":"10.26508","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1026-3305","authenticated-orcid":true,"given":"Mari","family":"Tenno","sequence":"first","affiliation":[{"name":"Department of Immune Regulation, The Research Center for Hepatitis and Immunology, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, 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