Extended Data Fig. 10: ILC3s restrain IL-23 mediated inflammation through CTLA-4.

Here we define a pathway of immune regulation in the large intestine. This pathway is activated by gut microbes and IL-23 in a FOXO1- and STAT3-dependent manner. ILC3-intrinsic CTLA-4 shapes the levels of co-inhibitory and co-stimulatory molecules on intestinal myeloid cells to support Tregs and restrict T effector (Teff) cells. Consequently, ILC3-intrinsic CTLA-4 function as a checkpoint to restrain the pathologic functions of IL-23, suggesting that disruption of these lymphocytes, which occurs in IBD, contributes to chronic inflammation.