Driven by a joint hypoxic microenvironment, HIF-1α-dependent induction of RORγt together with FoxP3 degradation is damaging to Treg cells and promotes Th17 cell generation (62) (Figure 2). This suggests that altered metabolism in the RA synovial microenvironment affects Th17/Treg axis, providing a feed-forward mechanism to amplify inflammation. The gene discussed is FOXP3; the disease is rheumatoid arthritis.