Mus musculus Raw sequence reads. Mus musculus

Innate lymphoid cells (ILCs) are critical for host defence and tissue repair. The transcription factor RORα is required for ILC2 development but is also highly expressed by ILC3s where its function remains poorly defined. Previously, we found that Rorasg/sg bone marrow transplant (BMT) mice were protected from Salmonella­-induced intestinal fibrosis due to defective ILC3 cytokine expression. In this study, we utilized whole transcriptome sequencing, which revealed the downregulation of ILC3 signature genes in RORα-deficient ILC3s following Salmonella infection. Moreover, Rorasg/sg ILC3s failed to express IL-17A following ex vivo IL-23 and IL-1β stimulation. Consistent with these observations, Rorasg/sgBMT mice were more susceptible to Citrobacter rodentium infection due to attenuated expression of IL-22 and impaired induction of antimicrobial peptides. Collectively, our data suggests that RORα plays a key role in preserving functional ILC3s by modulating their ability to integrate environmental cues to efficiently produce cytokines.