2013 Fiscal Year Final Research Report
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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| 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 |
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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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[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
Pages: 3180-8
DOI
Peer Reviewed
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