Immunoregulatory function of Lnk/Sh2b3, a common risk factor gene for immune, hematopoietic and cardiovascular diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial 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, 研究所, 免疫制御研究部長 (10242116)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 疾患関連遺伝子 / 自己免疫 / 高血圧 / 糖尿病 / シグナル伝達 / 骨髄増殖性疾患

Outline of Final Research Achievements

Mutations in the LNK/SH2B3 gene are found in myeloproliferative disease patients, and LNK/SH2B3 polymorphisms have been reported to be associated with several autoimmune diseases and cardiovascular diseases. The intracellular adaptor Lnk/Sh2b3 regulates cytokine signals that control lymphohematopoiesis, However, the functions of Lnk/Sh2b3 related to autoimmune inflammation or cardiovascular dysfunction have not been understood. We have revealed that the ability of DCs to support Th1 response was altered by Lnk-deficiency. We have shown that Lnk/Sh2b3 plays a role in preventing pathogenic expansion and activation of CD8+ T cells leading to intestinal tissue damage in Lnk-/- mice. IFN-gamma-producing CD8+ T cells were increased in kidney and arteries, resulting in increased susceptibility for hypertension. We also found that Lnk-/- mice showed impaired glucose tolerance that was largely depend on the abnormality of hematopoietic cells.

Free Research Field

免疫学