Control of the differentiation of regulatory T cells and TH 17 cells by the DNA-binding inhibitor Id3

Takashi Maruyama, Jun Li, Jose P. Vaque, Joanne E. Konkel, Weifeng Wang, Baojun Zhang, Pin Zhang, Brian F. Zamarron, Dongyang Yu, Yuntao Wu, Yuan Zhuang, J. Silvio Gutkind, Wanjun Chen

    Research output: Contribution to journalArticlepeer-review

    106 Citations (Scopus)

    Abstract

    The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4+ T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3+ regulatory T cells (Treg cells). We identify two transforming growth factor-β 21 (TGF-β 21)-dependent mechanisms that were vital for activation of Foxp3 transcription and were defective in Id3-/- CD4+ T cells. Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription. Id3 was required for relief of inhibition by the transcription factor GATA-3 at the Foxp3 promoter. Furthermore, Id3-/- T cells showed greater differentiation into the TH 17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-β 2-dependent manner to control Foxp3 expression and inhibit the development of TH 17 cells.

    Original languageEnglish
    Pages (from-to)86-95
    Number of pages10
    JournalNature Immunology
    Volume12
    Issue number1
    DOIs
    Publication statusPublished - 2011 Jan

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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