Spatial distribution of LTi-like cells in intestinal mucosa regulates type 3 innate immunity
Cristiane Sécca, Jennifer K. Bando, José Luís Fachi, Susan Gilfillan, Vincent Peng, Blanda Di Luccia, Marina Cella, Keely G. McDonald, Rodney D. Newberry, Marco Colonna
Abstract
Significance The lymphoid tissue inducer (LTi)-like cell is a specialized innate lymphocyte that produces cytokines that promote intestinal epithelial barrier integrity and protective immunity against pathogenic bacteria. Here, we report that the spatial positioning of LTi-like cells within intestinal mucosa enables them to receive signals that control their activity. Deletion of the LTi-like cell chemokine receptor CXCR5 displaced LTi-like cells from their natural niche in gut mucosa and enhanced their capacity to produce cytokines upon activation. LTi-like cell hyperresponsiveness in Cxcr5 -deficient mice strongly improved gut barrier integrity and protected mice during infection with the human opportunistic pathogen Clostridium difficile . Our findings demonstrate that the specialized positioning of LTi-like cells within the gut mucosa controls their activity and impacts protective immunity.