Homeostatic IL-23 receptor signaling limits Th17 response through IL-22–mediated containment of commensal microbiota

VFS Shih, J Cox, NM Kljavin… - Proceedings of the …, 2014 - National Acad Sciences
VFS Shih, J Cox, NM Kljavin, HS Dengler, M Reichelt, P Kumar, L Rangell, JK Kolls, L Diehl…
Proceedings of the National Academy of Sciences, 2014National Acad Sciences
Mammalian hosts are colonized with commensal microbes in various mucosal and epithelial
tissues, including the intestinal tract. In mice, the presence of segmented filamentous
bacteria (SFB) promotes Th17 differentiation and the development of autoimmune disease.
Here, we demonstrate that the IL-23 pathway dynamically regulates the abundance of SFB
as well as mucosal barrier function in the adult animal. Genetic or pharmacological
inactivation of the pathway selectively perturbs the abundance of a small group of …
Mammalian hosts are colonized with commensal microbes in various mucosal and epithelial tissues, including the intestinal tract. In mice, the presence of segmented filamentous bacteria (SFB) promotes Th17 differentiation and the development of autoimmune disease. Here, we demonstrate that the IL-23 pathway dynamically regulates the abundance of SFB as well as mucosal barrier function in the adult animal. Genetic or pharmacological inactivation of the pathway selectively perturbs the abundance of a small group of commensals, including SFB, and results in an impaired mucosal barrier. Defective barrier function leads to systemic dissemination of microbial products, provoking induction of the IL-23 pathway with dual consequences: IL-23 drives IL-22 production to reinforce mucosal barrier function and elicit antimicrobial activities, and it also drives the differentiation of Th17 cells in an attempt to combat escaped microbes in the lamina propria and in distal tissues. Thus, barrier defects generate a systemic environment that facilitates Th17 development.
National Acad Sciences