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• W3092326438 abstract "Abstract Hypoxia-inducible factor 1α (HIF-1α) and HIF-2α are master transcription factors that regulate cellular responses to hypoxia, but the exact function in regulatory T (Treg) cells is controversial. Here, we show that Treg cell development is normal in mice with Foxp3-specific knockout (KO) of HIF-1α or HIF-2α. However, HIF-2α-KO (but not HIF-1α-KO) Treg cells are functionally defective in suppressing effector T cell-induced colitis and inhibiting airway hypersensitivity. HIF-2α-KO Treg cells have enhanced reprogramming into IL-17-secreting cells. We show crosstalk between HIF-2α and HIF-1α, and that HIF-2α represses HIF-1α expression. HIF-1α is upregulated in HIF-2α-KO Treg cells and further deletion of HIF-1α restores the inhibitory function of HIF-2α-KO Treg cells. Mice with Foxp3-conditional KO of HIF-2α are resistant to growth of MC38 colon adenocarcinoma and metastases of B16F10 melanoma. Together, these results indicate that targeting HIF-2α to destabilize Treg cells might be an approach for regulating the functional activity of Treg cells." @default.
• W3092326438 created "2020-10-15" @default.
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• W3092326438 date "2020-10-06" @default.
• W3092326438 modified "2023-10-16" @default.
• W3092326438 title "HIF-2α is indispensable for regulatory T cell function" @default.
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• W3092326438 doi "https://doi.org/10.1038/s41467-020-18731-y" @default.
• W3092326438 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7538433" @default.
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• W3092326438 hasPublicationYear "2020" @default.
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