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2013 Fiscal Year Final Research Report

Commensal microbiota maintains gut homeostasis through epigenetic modification

Research Project

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Project/Area Number 24890293
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

FURUSAWA Yukihiro  東京大学, 医科学研究所, 特任助教 (80632306)

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)
Project Period (FY) 2012-08-31 – 2014-03-31
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
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.

  • Research Products

    (2 results)

All 2014 2013

All Journal Article (1 results) Presentation (1 results)

  • [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
    • Journal Title

      Nat. Immunol

      Volume: (in press)

  • [Presentation] Commensal microbiota shapes gut immune system through epigenetic modification2013

    • Author(s)
      Furusawa Y, Obata Y, Sharif J, Hori S, Ohno H, Koseki H, Hase K
    • Organizer
      International Congress of Mucosal Immunology
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      20130717-20

URL: 

Published: 2015-07-16  

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