Here, we have further demonstrated that elevated HIF-1α in HIF-2α-KO Treg cells contributes to the instability of HIF-2α-KO Treg cells in vivo, as further knockout of HIF-1α restored the function of HIF-2α-KO tTreg cells and HIF-2α-KO iTreg cells in suppressing effector T cells-induced colitis and allergen-triggered airway inflammation, respectively (Fig. 6). This evidence concerns the gene EPAS1 and colitis.