Details

Autor(en) / Beteiligte

• Shih, Vincent Feng-Sheng
• Cox, Jennifer
• Kljavin, Noelyn M.
• Dengler, Hart S.
• Reichelt, Mike
• Kumar, Pawan
• Rangell, Linda
• Kolls, Jay K.
• Diehl, Lauri
• Ouyang, Wenjun
• Ghilardi, Nico

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2014-09, Vol.111 (38), p.13942-13947

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2014

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Significance Commensal microbiota are known to be required for the elicitation of host Th17 responses, which may mediate autoimmune diseases. Here, we demonstrate that the IL-23 pathway dynamically regulates the abundance of certain commensals and maintains barrier function. Barrier disruption results in systemic dissemination of microbial products, which invokes the IL-23 pathway, with both beneficial and potentially deleterious consequences. Through induction of IL-22, IL-23 contributes to barrier repair, and through induction of the Th17 response, it aims to neutralize escaped commensal microbes. Thus, barrier disruption results in a pro-Th17 environment in which not only antimicrobial but also potentially antihost Th17 cells can develop. 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.