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HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis.
MedLine Citation:
PMID:  22457366     Owner:  NLM     Status:  Publisher    
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 an 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.
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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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-27
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  -     ISSN:  1938-3673     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
*Department of Internal Medicine, National Defense Medical College, Saitama, Japan;
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