| First Author | Higashiyama M | Year | 2012 |
| Journal | J Leukoc Biol | Volume | 91 |
| Issue | 6 | Pages | 901-9 |
| PubMed ID | 22457366 | Mgi Jnum | J:184909 |
| Mgi Id | MGI:5426728 | Doi | 10.1189/jlb.1011518 |
| Citation | Higashiyama M, et al. (2012) HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis. J Leukoc Biol 91(6):901-9 |
| abstractText | 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-1alpha 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. |
