CD40 and colitis: Irrespective of the afore mentioned strategies, fine-balancing of any therapeutic interference with ILC3-driven IL-22 secretion and individual patient selection will be of critical importance, since next to its protective effects on IECs, a detrimental potential of IL-22 on the epithelial barrier has been observed in selected mouse models, as for instance in the anti-CD40-induced innate colitis model (67).