Other
18 Authors
- Barbi J,
- Pardoll DM,
- Bordman Z,
- Zeller K,
- Pan F,
- Dang EV,
- Yang HY,
- Dang CV,
- Yu H,
- Zheng Y,
- Fu J,
- Jinasena D,
- Topalian SL,
- Shimoda L,
- Yen HR,
- Semenza GL,
- Kim Y,
- Luo W
| First Author | Dang EV | Year | 2011 |
| Journal | Cell | Volume | 146 |
| Issue | 5 | Pages | 772-84 |
| PubMed ID | 21871655 | Mgi Jnum | J:176230 |
| Mgi Id | MGI:5289736 | Doi | 10.1016/j.cell.2011.07.033 |
| Citation | Dang EV, et al. (2011) Control of T(H)17/T(reg) Balance by Hypoxia-Inducible Factor 1. Cell 146(5):772-84 |
| abstractText | T cell differentiation into distinct functional effector and inhibitory subsets is regulated, in part, by the cytokine environment present at the time of antigen recognition. Here, we show that hypoxia-inducible factor 1 (HIF-1), a key metabolic sensor, regulates the balance between regulatory T cell (T(reg)) and T(H)17 differentiation. HIF-1 enhances T(H)17 development through direct transcriptional activation of RORgammat and via tertiary complex formation with RORgammat and p300 recruitment to the IL-17 promoter, thereby regulating T(H)17 signature genes. Concurrently, HIF-1 attenuates T(reg) development by binding Foxp3 and targeting it for proteasomal degradation. Importantly, this regulation occurs under both normoxic and hypoxic conditions. Mice with HIF-1alpha-deficient T cells are resistant to induction of T(H)17-dependent experimental autoimmune encephalitis associated with diminished T(H)17 and increased T(reg) cells. These findings highlight the importance of metabolic cues in T cell fate determination and suggest that metabolic modulation could ameliorate certain T cell-based immune pathologies. |
