2013 Fiscal Year Final Research Report
Commensal microbiota maintains gut homeostasis through epigenetic modification
| Project/Area Number |
24890293
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Research Collaborator |
ENDO Takaho 理化学研究所, 統合生命医科学研究所統合ゲノミクスグループ, 上級研究員 (40384862)
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | エピジェネティクス / 制御性T細胞 / DNAメチル化 / 炎症性腸疾患 |
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| Research Abstract |
Intestinal regulatory T (Treg) cells are necessary for suppression of excessive immune response to commensal bacteria. However, the molecular machinery controlling intestinal Treg cell homeostasis remains largely unknown. Here we report that colonization of germ-free mice with gut microbiota upregulated the expression of the DNA methylation adaptor Uhrf1 in Treg cells. Cd4creUhrf1fl/fl mice were defective in proliferation and functional maturation of colonic Treg cells. Uhrf1 deficiency de-repressed cyclin-dependent kinase inhibitor Cdkn1a due to hypomethylation of its promoter region, resulting in cell-cycle arrest of Treg cells. As a consequence, Cd4creUhrf1fl/fl mice spontaneously developed severe colitis. Thus, Uhrf1-dependent epigenetic silencing of Cdkn1a is required for the maintenance of gut immune homeostasis. This mechanism enforces symbiotic host-microbe interactions without an inflammatory response.
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[Journal Article] Epigenetic regulator Uhrf1 is critical for functional expansion of colonic regulatory T cells2014
Author(s)
Obata Y, Furusawa Y , Endo TA, Sharif J, Takahashi D, Atarashi K, Onawa S, Fujimura Y, Takahashi M, Ikawa T, Otsubo T, Kawamura YI, Dohi T, Tajima S, Ohara O, Honda K, Hori S, Ohno H, Koseki H, Hase K
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Journal Title
Nat. Immunol
Volume: (in press)
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