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.
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T cells present in inflammatory lesions in inflammatory bowel disease and rheumatoid arthritis express Hif-1α.
“T cells present in inflammatory lesions in inflammatory bowel disease (Crohn’s disease and ulcerative colitis) [34] and rheumatoid arthritis [35] express Hif-1α.”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [34]
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- Authors
- 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.
- Affiliations
- National Defense Medical College (JP)
- Keio University (JP)
- Waseda University (JP)
- Corresponding author
- Higashiyama, Masaaki
- ORCID
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-06-01
- Volume
- 91
- Issue
- 6
- Pages
- 901-909
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2130035222
- Cited by
- 68
- References
- 38
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 7 · 2017: 3 · 2016: 3 · 2015: 9 · 2014: 7 · 2013: 1 · 2012: 1
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NDMC
- Health and Labor Sciences Research
- Ministry of Health, Labor and Welfare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- HIF-1α, T cells, inflammatory bowel disease, DSS-induced colitis, hypoxia, regulatory T cells, Th17 cells, Th1 cells, colonic inflammation, cytokine balance, intestinal inflammation
- MeSH terms
- Animals, Colitis, Colon, Disease Models, Animal, Female, Humans, Intestinal Mucosa, Male, Dextran Sulfate, Mice, Knockout, Mice, Hypoxia-Inducible Factor 1, Th17 Cells
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