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

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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 1

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Keywords

  • DSS colitis
  • IBD
  • Th1
  • Th17
  • Treg

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Higashiyama, M., Hokari, R., Hozumi, H., Kurihara, C., Ueda, T., Watanabe, C., Tomita, K., Nakamura, M., Komoto, S., Okada, Y., Kawaguchi, A., Nagao, S., Suematsu, M., Goda, N., & Miura, S. (2012). HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis. Journal of Leukocyte Biology, 91(6), 901-909. https://doi.org/10.1189/jlb.1011518