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

    Research output: Contribution to journalArticle

    28 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

    Fingerprint

    Dextran Sulfate
    Colitis
    T-Lymphocytes
    Mucous Membrane
    Inflammation
    Eragrostis
    Up-Regulation
    Epithelium
    Immunohistochemistry
    Cytokines

    Keywords

    • DSS colitis
    • IBD
    • Th1
    • Th17
    • Treg

    ASJC Scopus subject areas

    • Cell Biology
    • Immunology

    Cite this

    Higashiyama, M., Hokari, R., Hozumi, H., Kurihara, C., Ueda, T., Watanabe, C., ... 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

    HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis. / Higashiyama, Masaaki; Hokari, Ryota; Hozumi, Hideaki; Kurihara, Chie; Ueda, Toshihide; Watanabe, Chikako; Tomita, Kengo; Nakamura, Mitsuyasu; Komoto, Shunsuke; Okada, Yoshikiyo; Kawaguchi, Atsushi; Nagao, Shigeaki; Suematsu, Makoto; Goda, Nobuhito; Miura, Soichiro.

    In: Journal of Leukocyte Biology, Vol. 91, No. 6, 06.2012, p. 901-909.

    Research output: Contribution to journalArticle

    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, vol. 91, no. 6, pp. 901-909. https://doi.org/10.1189/jlb.1011518
    Higashiyama M, Hokari R, Hozumi H, Kurihara C, Ueda T, Watanabe C et al. HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis. Journal of Leukocyte Biology. 2012 Jun;91(6):901-909. https://doi.org/10.1189/jlb.1011518
    Higashiyama, Masaaki ; Hokari, Ryota ; Hozumi, Hideaki ; Kurihara, Chie ; Ueda, Toshihide ; Watanabe, Chikako ; Tomita, Kengo ; Nakamura, Mitsuyasu ; Komoto, Shunsuke ; Okada, Yoshikiyo ; Kawaguchi, Atsushi ; Nagao, Shigeaki ; Suematsu, Makoto ; Goda, Nobuhito ; Miura, Soichiro. / HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis. In: Journal of Leukocyte Biology. 2012 ; Vol. 91, No. 6. pp. 901-909.
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