2016 Fiscal Year Final Research Report
Novel control mechanism by autoimmune disease-related gene Lnk/Sh2b3 in diabetic pathogenesis
Project/Area Number |
15K19082
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Experimental pathology
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Research Institution | National Center for Global Health and Medicine |
Principal Investigator |
Mori Taizo 国立研究開発法人国立国際医療研究センター, 免疫制御研究部, 研究員 (40625307)
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Keywords | 2型糖尿病 / 免疫学 / シグナル伝達 / サイトカイン / 自己免疫疾患関連遺伝子 |
Outline of Final Research Achievements |
Lnk/Sh2b3 is an adaptor protein that negatively regulates cytokine signaling in lymphopoiesis. A missense variant within the LNK/SH2B3 gene has been reported to be a risk variant for several autoimmune diseases including diabetes. We found that glucose tolerance and insulin responses were impaired in Lnk KO mice. Moreover, immune cells such as group 1 innate lymphoid cells and M1 macrophages accumulated in adipose tissues. When Lnk KO mice were crossed with Il15 KO mice or depleted of G1-ILCs but not CD8+ T cells, glucose intolerance and adipose inflammation were ameliorated. Lnk KO G1-ILCs showed activated phenotypes as well as enhanced reactivity for IL-15, and administration of a JAK3 inhibitor improved glucose tolerance. Thus, Lnk/Sh2b3 controls homeostasis in adipose tissues and reduces the risk for onset of diabetes by regulating the expansion and activation of IL-15-dependent adipose G1-ILCs.
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Free Research Field |
実験病理学
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