| First Author | Hsu TS | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 5005 |
| PubMed ID | 33024109 | Mgi Jnum | J:303356 |
| Mgi Id | MGI:6471377 | Doi | 10.1038/s41467-020-18731-y |
| Citation | Hsu TS, et al. (2020) HIF-2alpha is indispensable for regulatory T cell function. Nat Commun 11(1):5005 |
| abstractText | Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha 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-1alpha or HIF-2alpha. However, HIF-2alpha-KO (but not HIF-1alpha-KO) Treg cells are functionally defective in suppressing effector T cell-induced colitis and inhibiting airway hypersensitivity. HIF-2alpha-KO Treg cells have enhanced reprogramming into IL-17-secreting cells. We show crosstalk between HIF-2alpha and HIF-1alpha, and that HIF-2alpha represses HIF-1alpha expression. HIF-1alpha is upregulated in HIF-2alpha-KO Treg cells and further deletion of HIF-1alpha restores the inhibitory function of HIF-2alpha-KO Treg cells. Mice with Foxp3-conditional KO of HIF-2alpha are resistant to growth of MC38 colon adenocarcinoma and metastases of B16F10 melanoma. Together, these results indicate that targeting HIF-2alpha to destabilize Treg cells might be an approach for regulating the functional activity of Treg cells. |
