Balancing acts by HIF

The induced polarization of T_reg cells and interleukin 17 (IL-17)-producing helper T cells (T_H17 cells) requires transforming growth factor-b, and there is plasticity between these two polarized states. In Cell, Dang et al. provide evidence that the transcription factor HIF-1 (hypoxia-inducible factor 1) contributes to T_H17 polarization and the suppression of T_reg differentiation. HIF-1-deficient cells have minimal expression of the transcription factor RORgt and IL-17 under T_H17-polarizing conditions and instead have higher expression of the transcription factor Foxp3. Enforced expression of HIF-1a alone induces a T_H17 phenotype. HIF-1a directly binds the locus encoding RORgt, but its upregulation of the genes encoding IL-17 and the receptor for IL-23 requires binding of DNA by RORgt and the histone acetyltransferase p300. Conversely, the interaction of HIF-1a with Foxp3 targets the latter for proteasome-mediated degradation. Hypoxia further enhances these polarized responses in T cells. These findings suggest oxygen tension and other metabolic cues sensed by HIF-1a can modulate the balance of T_reg cells to T_H17 cells.

Cell (2 September 2011) doi:10.1016/j.cell.2011.07.033