Function of a risk factor gene common to autoimmune diseases and life-style related diseases
Project/Area Number |
22590446
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | Research Institute, International Medical Center of Japan |
Principal Investigator |
TAKAKI Satoshi 独立行政法人国立国際医療研究センター, 研究所 免疫制御研究部, 部長 (10242116)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 自己免疫 / 免疫寛容 / 疾患関連遺伝子 / アダプター蛋白質 |
Research Abstract |
The intracellular adaptor Lnk/Sh2b3 regulates cytokine signals that control lymphohematopoiesis. In humans, mutations in the LNK/SH2B3 gene are found in myeloproliferative disease patients, and LNK/SH2B3 polymorphisms have been demonstrated to be associated with celiac disease and autoimmune diabetes. In this study, we revealed a previously unrecognized function of Lnk/Sh2b3 in preventing the accumulation of inflammatory CD8+ T cells and intestinal villous atrophy. Generation of an Lnk-Venus reporter mouse revealed expression of Lnk/Sh2b3 in mature T cells and dendritic cells. CD44+CD8+ T cells were increased in Lnk-/- mice, and many mice exhibited signs of villous atrophy in the small intestine. Lnk-/- CD8+ T cells survived longer and proliferated even in non-lymphopenic host animals in response to IL-15. Transfer of Lnk-/- CD44hiCD8+ T cells together with wild-type CD4+ T cells into RAG2-deficient mice recapitulated villous atrophy in ileum. Our results provide for the first time a missing link between Lnk/Sh2b3 and autoimmune-like tissue destruction responses.
|
Report
(4 results)
Research Products
(37 results)
-
-
-
[Journal Article] Structural basis of interleukin-5 dimer recognition by its alpha receptor2012
Author(s)
Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Ikutani M., Takaki S., Sakamoto K., Hara-Yokoyama M., Shirouzu M., Takatsu K., Yokoyama S
-
Journal Title
Protein Sci
Volume: 21
Issue: 6
Pages: 850-864
DOI
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Lnk-dependent axis of SCF-cKit signal for osteogenesis in bone fracture healing.2010
Author(s)
Matsumoto T, Ii M, Nishimura H, Shoji T, Mifune Y, Kawamoto A, Kuroda R, Fukui T, Kawakami Y, Kuroda T, Kwon SM, Iwasaki H, Horii M, Yokoyama A, Oyamada A, Lee SY, Hayashi S, Kurosaka M, Takaki S, Asahara T
-
Journal Title
J Exp Med
Volume: 207
Issue: 10
Pages: 2207-2223
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-