Spatiotemporal regulation of thymic Treg production by Rap1GTPase
| Project/Area Number |
16K08849
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Kansai Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 制御性T細胞 / 胸腺 / インテグリン / 組織培養 / イメージング / Rap1 / 負の選択 / 制御T細胞 / T細胞分化 / 免疫学 / 免疫寛容・自己免疫 / Treg |
|---|
| Outline of Final Research Achievements |
Regulatory T cells (Treg) are crucial for various immune regulation but their development is still elusive. To track the development of thymic Treg, we established thymic slice culture system for induction of antigen-specific Treg even without additional cytokine supplements. This revealed the dynamics of thymic Treg development and its regulation by doses of antigen. Previous studies suggest the involvement of integrin-mediated adhesion and signaling in Treg production but were still unknown. We examined the Treg production of thymocytes deficient for Rap1,a master regulator of integrin activation, and found that Rap1-deficient thymocytes impaired migration within thymic tissues and fail to produce Treg efficiently, suggesting that Rap1-mediated integrin activation is vital for Treg-development.
|
| Academic Significance and Societal Importance of the Research Achievements |
制御性T細胞は自己免疫や炎症の抑制、癌による免疫抑制に深くかかわっている。よって制御性T細胞を標的とした創薬は、上記の病気を克服するために重要である。本研究によりex vivoで制御性T細胞を誘導する系を確立したことにより、in vitroの実験系よりも生体に近い環境で制御性T細胞の産生を検討することができるようになった。この実験系を用いて制御性T細胞を標的とした抗体や低分子化合物の探索に応用できる可能性がある。また、この実験系を用いて胸腺細胞のRap1接着シグナルの阻害が制御性T細胞の産生を低下させることを明らかにし、制御性T細胞を標的する創薬の候補としてRap1シグナルの可能性を提示した。
|
Report
(4 results)
Research Products
(13 results)
-
-
-
-
[Journal Article] NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization.2017
Author(s)
Kondo, N., Ueda, Y., Kita, T., Ozawa, M., Tomiyama, T., Yasuda, K., Lim, D.S. and Kinashi, T.
-
Journal Title
Molecular and cellular biology
Volume: 37
Pages: 00424-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
