238 : Homeostatic IL23R signaling limits Th17 responses through IL22-mediated containment of commensal microbiota

Mammalian hosts are colonized with commensal microbes in various mucosal and epithelial tissues, including the intestinal tract. Disruption of the physiological barriers that prevent these organisms from disseminating outside their assigned niches leads to inflammatory responses. Using segmented filamentous bacteria (SFB) as a sentinel species, we demonstrate that the IL-23/IL-22 pathway dynamically and selectively modulates the relative abundance of certain commensals in the adult animal. Genetic or pharmacological inactivation of the pathway results in defective barrier function, leading to systemic microbial dissemination and enhanced TH17 responses in distal tissues. Furthermore, we demonstrate suppression of TH17 responses in wild-type animals upon activation of the IL-22 pathway. Our data therefore suggests that IL-23/IL-22 pathway is of critical importance for normal immune homeostasis through the maintenance of mucosal barrier function.