{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(12)"],"submitter":["Tenno M"],"pubmed_abstract":["The Lnk/Sh2b3 adaptor protein functions as a regulatory molecule for cytokine signaling in lymphohematopoiesis. A missense variant of the LNK/SH2B3 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 Lnk -/- mice showed increased susceptibility to diabetes following treatment with fairly low doses of streptozotocin, manifested by hyperglycemia and insulitis accompanied by accumulation of CD8+ T-cells and loss of pancreatic β cells. The high susceptibility of Lnk -/- mice to islet damage was abolished in crosses with Rag2 -/- mice lacking lymphocytes or MyD88 -/- mice carrying various defects in activation of innate immune cells. In Lnk -/- 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 β 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."],"journal":["Life science alliance"],"pagination":["e202503332"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12486559"],"repository":["biostudies-literature"],"pubmed_title":["Lnk/Sh2b3 regulates initiation and severity of autoimmune insulitis and contributes to diabetes risk."],"pmcid":["PMC12486559"],"pubmed_authors":["Takaki S","Tenno M"],"additional_accession":[]},"is_claimable":false,"name":"Lnk/Sh2b3 regulates initiation and severity of autoimmune insulitis and contributes to diabetes risk.","description":"The Lnk/Sh2b3 adaptor protein functions as a regulatory molecule for cytokine signaling in lymphohematopoiesis. A missense variant of the LNK/SH2B3 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 Lnk -/- mice showed increased susceptibility to diabetes following treatment with fairly low doses of streptozotocin, manifested by hyperglycemia and insulitis accompanied by accumulation of CD8+ T-cells and loss of pancreatic β cells. The high susceptibility of Lnk -/- mice to islet damage was abolished in crosses with Rag2 -/- mice lacking lymphocytes or MyD88 -/- mice carrying various defects in activation of innate immune cells. In Lnk -/- 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 β 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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-04T00:03:24.254Z","creation":"2026-05-03T03:11:33.943Z"},"accession":"S-EPMC12486559","cross_references":{"pubmed":["41027725"],"doi":["10.26508/lsa.202503332"]}}