| Project/Area Number |
15K19082
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Experimental pathology
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2015-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| 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 / 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.
|
