In a gain-of-function experiment, we examined the impact of hyperoxia on CDI in mice overexpressing HIF-1α in ILC3 and T cells due to conditional deletion of VHL (Figure 7h, i), an E3-ubiquitin ligase that binds and downregulates HIF-1α and HIF-2α in the presence of oxygen.51 These VhlΔRorc mice showed higher levels of ILC3 (of the NCR− subtypes) and increased expression of RORγt, IL-22, and IL-17 in the colonic LP at a steady state (Fig. S8f-h). Here, VHL is linked to clostridium difficile infection.