title: HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis.
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.
authors.affiliation: Department of Internal Medicine, National Defense Medical College, Saitama, Japan. dr22055@ndmc.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashiyama
authors.forename: Ryota
authors.initials: R
authors.lastname: Hokari
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hozumi
authors.forename: Chie
authors.initials: C
authors.lastname: Kurihara
authors.forename: Toshihide
authors.initials: T
authors.lastname: Ueda
authors.forename: Chikako
authors.initials: C
authors.lastname: Watanabe
authors.forename: Kengo
authors.initials: K
authors.lastname: Tomita
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Komoto
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Okada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nagao
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D003106:Colon / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D051793:Hypoxia-Inducible Factor 1; D016264:Dextran Sulfate