HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis

Masaaki Higashiyama*, Ryota Hokari, Hideaki Hozumi, Chie Kurihara, Toshihide Ueda, Chikako Watanabe, Kengo Tomita, Mitsuyasu Nakamura, Shunsuke Komoto, Yoshikiyo Okada, Atsushi Kawaguchi, Shigeaki Nagao, Makoto Suematsu, Nobuhito Goda, Soichiro Miura

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

HIF-1 is active in hypoxia, such as inflamed mucosa, and HIF-1 in epithelium has been reported to control inflamed mucosa in IBD models. Although T cells play an important role for pathogenesis of IBD, the function of HIF-1 in T cells remains to be elucidated. We aimed to clarify the function of HIF-1 in T cells in IBD with focus on the balance between Treg and Teff. Double immunohistochemistry of colonic mucosa in IBD patients showed that HIF-1 was expressed in T cells infiltrating the inflamed mucosa, suggesting that HIF-1 in T cells is involved in the pathogenesis. DSS administration to T cell-specific HIF-1α KO mice showed more severe colonic inflammation than control mice with the up-regulation of Th1 and Th17. Hypoxic stimulation in vitro increased Treg activation in WT T cells but not in HIF-1-deleted T cells. In contrast, hypoxic stimulation increased Th17 activation, and the degree was higher in HIF-1-deleted cells than in control cells. These results show that hypoxia controls intestinal inflammation by regulating cytokine balance in a HIF-1-dependent manner, suggesting that strengthening HIF-1 induction in T cells at the sites of inflammation might be a therapeutic strategy for IBD regulation.

Original languageEnglish
Pages (from-to)901-909
Number of pages9
JournalJournal of Leukocyte Biology
Volume91
Issue number6
DOIs
Publication statusPublished - 2012 Jun

Keywords

  • DSS colitis
  • IBD
  • Th1
  • Th17
  • Treg

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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