Roles of disease associated gene Lnk/Sh2b3 in inflammation.
| 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
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| 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 / 自己免疫 / 糖尿病 / 脂肪炎症 |
|---|
| 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.
|
| 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。
|
Report
(4 results)
Research Products
(6 results)
