Akt1-mediated Gata3 phosphorylation controls the repression of IFNÎ 3 in memory-type Th2 cells

Hiroyuki Hosokawa, Tomoaki Tanaka, Yusuke Endo, Miki Kato, Kenta Shinoda, Akane Suzuki, Shinichiro Motohashi, Masaki Matsumoto, Keiichi I. Nakayama, Toshinori Nakayama

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12 Citations (Scopus)

Abstract

Th2 cells produce Th2 cytokines such as IL-4, IL-5 and IL-13, but repress Th1 cytokine IFNÎ 3. Recent studies have revealed various distinct memory-type Th2 cell subsets, one of which produces a substantial amount of IFNγ 3 in addition to Th2 cytokines, however it remains unclear precisely how these Th2 cells produce IFNγ 3. 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 3 expression in IFNγ 3-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 3 expression in memory Th2 cells.

Original languageEnglish
Article number11289
JournalNature communications
Volume7
DOIs
Publication statusPublished - Apr 7 2016

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Hosokawa, H., Tanaka, T., Endo, Y., Kato, M., Shinoda, K., Suzuki, A., Motohashi, S., Matsumoto, M., Nakayama, K. I., & Nakayama, T. (2016). Akt1-mediated Gata3 phosphorylation controls the repression of IFNÎ 3 in memory-type Th2 cells. Nature communications, 7, [11289]. https://doi.org/10.1038/ncomms11289