Roles of disease associated gene Lnk/Sh2b3 in inflammation.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08802
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Takaki Satoshi 国立研究開発法人国立国際医療研究センター, その他部局等, 免疫制御研究部長 (10242116)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: アダプター蛋白質 / 疾患関連遺伝子 / 耐糖能異常 / 慢性炎症 / サイトカイン / リンパ球

Outline of Final Research Achievements

Lymphocyte-specific adaptor protein, Lnk (also known as Sh2b3), is primarily expressed in hematopoietic cells where it functions as a negative regulator of cytokine signaling and cell proliferation. Single nucleotide polymorphisms in Lnk are associated with autoimmune and cardiovascular disorders, but the mechanism by which Lnk contributes to those diseases is unknown. We found that Lnk-/- mice showed glucose intolerance and insulin resistance, and the expansion and activation of group 1-innate lymphoid cells (G1-ILCs) in adipose tissues. The results delineate a primary mechanism by which Lnk/Sh2b3 regulates homeostatic processes in adipose tissues and also how it affects the risk of diabetes by regulating the expansion and activation of adipose G1-ILCs and their contribution to insulin resistance.

Free Research Field

免疫学　実験病理学

Academic Significance and Societal Importance of the Research Achievements

Lnk欠損あるいは機能低下は、脂肪組織の免疫細胞活性化による脂肪組織炎症を誘発して耐糖能異常を呈すること、糖尿病発病の閾値を低下させ病態形成に寄与することが考えられる。標的細胞は脂肪組織のG1-ILCであり、今回の知見は、脂肪組織の恒常性維持における新しい制御機構、Lnk/SH2B3依存性のG1-ILC機能と脂肪炎症との関連を明らかにするものである。