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Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells

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  • Hiroyuki Hosokawa

    (Graduate School of Medicine, Chiba University)

  • Tomoaki Tanaka

    (Graduate School of Medicine, Chiba University
    Graduate School of Medicine, Chiba University
    AMED-CREST, AMED)

  • Yusuke Endo

    (Graduate School of Medicine, Chiba University)

  • Miki Kato

    (Graduate School of Medicine, Chiba University)

  • Kenta Shinoda

    (Graduate School of Medicine, Chiba University)

  • Akane Suzuki

    (Graduate School of Medicine, Chiba University)

  • Shinichiro Motohashi

    (Graduate School of Medicine, Chiba University)

  • Masaki Matsumoto

    (Medical Institute of Bioregulation, Kyushu University)

  • Keiichi I. Nakayama

    (Medical Institute of Bioregulation, Kyushu University)

  • Toshinori Nakayama

    (Graduate School of Medicine, Chiba University
    AMED-CREST, AMED)

Abstract

Th2 cells produce Th2 cytokines such as IL-4, IL-5 and IL-13, but repress Th1 cytokine IFNγ. Recent studies have revealed various distinct memory-type Th2 cell subsets, one of which produces a substantial amount of IFNγ in addition to Th2 cytokines, however it remains unclear precisely how these Th2 cells produce IFNγ. We herein show that phosphorylation of Gata3 at Ser308, Thr315 and Ser316 induces dissociation of a histone deacetylase Hdac2 from the Gata3/Chd4 repressive complex in Th2 cells. We also identify Akt1 as a Gata3-phosphorylating kinase, and the activation of Akt1 induces derepression of Tbx21 and Ifng expression in Th2 cells. Moreover, T-bet-dependent IFNγ expression in IFNγ-producing memory Th2 cells appears to be controlled by the phosphorylation status of Gata3 in human and murine systems. Thus, this study highlights the molecular basis for posttranslational modifications of Gata3 that control the regulation of IFNγ expression in memory Th2 cells.

Suggested Citation

  • Hiroyuki Hosokawa & Tomoaki Tanaka & Yusuke Endo & Miki Kato & Kenta Shinoda & Akane Suzuki & Shinichiro Motohashi & Masaki Matsumoto & Keiichi I. Nakayama & Toshinori Nakayama, 2016. "Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11289
    DOI: 10.1038/ncomms11289
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