Role of mDia, a polymerization factor, in Treg differentiation
| Project/Area Number |
17K08591
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kyoto University |
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Principal Investigator |
Thumkeo Dean 京都大学, 医学研究科, 特定准教授 (40372594)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 制御性T細胞 / アクチン細胞骨格 / mDia / Treg / 免疫寛容 / 薬理学 / 免疫学 / 細胞・組織 |
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| Outline of Final Research Achievements |
1) Using mDia1/3 DKO mice, we found that mDia1/3 promoted differentiation of nTreg cells. 2) We induced differentiation of iTreg cells in vitro and found that mDia1 / 3 is also essential for iTreg differentiation. 3) When we stimulated TCR signaling that is critical for Treg differntiation, we found that the F-actin structure and kinetics of mDia1/3-deficient T cells were significantly inhibited. 4) For gene expression analysis, we generated mDia1/3 cDKO mice in which Treg cells were fluorescently labeled with EGFP.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究はTreg細胞の分化にアクチン重合因子mDiaが不可欠であることを見出した。さらに、Treg細胞の分化におけるmDiaの分子作用機序の一端を明らかにし、これまでの研究によって明らかになっているTreg細胞分化メカニズムの知見と統合させることにより、Treg細胞の分化及び機能発現の理解を深めることができると考えている。さらには、臨床的な観点から、Treg細胞の分化あるいは機能発現に関わる分子とその働くメカニズムの解明は将来的に自己免疫疾患に応用できる新しい免疫抑制薬の開発につながる可能性があり、非常に意義があると考える。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.2020
Author(s)
Thumkeo, D., Katsura, Y., Nishimura, Y., Kanchanawong, P., Tohyama, K., Ishizaki, T., Kitajima, S., Takahashi, C., Hirata, T., Watanabe, N., Krummel, M. F., and Narumiya, S.
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Journal Title
Sci. Adv.
Volume: 6
Issue: 1
Pages: 2432-2432
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] LPA Induces Keratinocyte Differentiation and Promotes Skin Barrier Function through the LPAR1/LPAR5-RHO-ROCK-SRF Axis.2018
Author(s)
Sumitomo A, Siriwach R, Thumkeo D, Ito K, Nakagawa R, Tanaka N, Tanabe K, Watanabe A, Kishibe M, Ishida-Yamamoto A, Honda T, Kabashima K, Aoki J, Narumiya S.
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Journal Title
J Invest Dermatol. 2018 Nov 14.
Volume: pii: S0022-202X(18)32815-X.
Issue: 5
Pages: 1010-1022
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] mDia1/3 generate cortical F-actin meshwork in Sertoli cells that is continuous with contractile F-actin bundles and indispensable for spermatogenesis and male fertility.2018
Author(s)
S. Sakamoto, D. Thumkeo, H. Ohta, Z. Zhang, S.R. Huang, P. Kanchenawong, T. Fuu, S. Watanabe, K. Shimada, Y. Fujihara, S. Yoshida, M. Ikawa, N. Watanabe, M. Saitou and S. Narumiya
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Journal Title
Plos Biology
Volume: 16
Issue: 9
Pages: e2004874-e2004874
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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