Elucidating the molecular basis of regulatory T cell differentiation
| Project/Area Number |
23390123
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
HORI Shohei 独立行政法人理化学研究所, 統合生命医科学研究センター, チームリーダー (50392113)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
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| Keywords | 細胞分化 / 細胞運命 / 分化可塑性 / 制御性T細胞 / 転写因子 / 自己免疫寛容 / 自己免疫 / 免疫制御 / 可塑性 |
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| Research Abstract |
The emerging notion of environment-induced reprogramming of Foxp3+ regulatory T (Treg) cells into helper T (Th) cells remains controversial. By genetic fate mapping or adoptive transfers, we have identified a minor population of non-regulatory Foxp3+ T cells exhibiting promiscuous and transient Foxp3 expression, which gives rise to Foxp3- Th cells and selectively accumulates in inflammatory cytokine milieus or in lymphopenic environments including those in early ontogeny. In contrast, Treg cells do not undergo reprogramming under those conditions irrespectively of their thymic or peripheral origins. Moreover, while a few Treg cells transiently lose Foxp3 expression, such "latent" Treg cells retain memory of Foxp3 expression and suppressive function. Our study establishes that Treg cells constitute a stable cell lineage, whose committed state in a changing environment is ensured by DNA demethylation of the Foxp3 locus irrespectively of ongoing Foxp3 expression.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus2013
Author(s)
Toker A, Engelbert D, Garg G, Polansky Geffers R, Giehr P, Schallenberg S, Kretschmer K, Olek S, Walter J, Weiss S, Hori S, Hamann A, Huehn J
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Journal Title
J Immunol
Volume: 190
Issue: 7
Pages: 3180-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Commensal microbe-derived butyrate induces colonic regulatory T cells2013
Author(s)
Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A. Endo, Gaku Nakato, Daisuke Takahashi, Yumiko Nakanishi, Chikako Uetake, Keiko Kato, Tamotsu Kato, Masumi Takahashi, Noriko N. Fukuda, Shinnosuke Murakami, Eiji Miyauchi, Shingo Hino, Koji Atarashi, Satoshi Onawa, Yumiko Fujimura, Trevor Lockett, Julie M. Clarke, David L. Topping, Masaru Tomita, Shohei Hori, Osamu Ohara, Tatsuya Morita, Haruhiko Koseki, J un Kikuchi, Kenya Honda, Koji Hase and Hiroshi Ohno
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Journal Title
Nature
Volume: 506
Issue: 7480
Pages: 446-450
DOI
Related Report
Peer Reviewed
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[Journal Article] Prostaglandin E2-prostoglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression2011
Author(s)
Kitipong Soontrapa, Tetsuya Honda, Daiji Sakata, Chengcan Yao, Takako Hirata, Shohei Hori, Toshiyuki Matsuoka, Yoshihiro Kita, Takao Shimizu, Kenji Kabashima, Shuh Narumiya
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Journal Title
Proc Natl Acad Sci U S A
Volume: 108
Issue: 16
Pages: 668-667
DOI
Related Report
Peer Reviewed
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