Th17 cytokines and the gut mucosal barrier

Abstract

Local immune responses serve to contain infections by pathogens to the gut while preventing pathogen dissemination to systemic sites. Several subsets of T cells in the gut (T-helper 17 cells, gammadelta T cells, natural killer (NK), and NK-T cells) contribute to the mucosal response to pathogens by secreting a subset of cytokines including interleukin (IL)-17A, IL-17F, IL-22, and IL-26. These cytokines induce the secretion of chemokines and antimicrobial proteins, thereby orchestrating the mucosal barrier against gastrointestinal pathogens. While the mucosal barrier prevents bacterial dissemination from the gut, it also promotes colonization by pathogens that are resistant to some of the inducible antimicrobial responses. In this review, we describe the contribution of Th17 cytokines to the gut mucosal barrier during bacterial infections.

Fig. 1

Th17 cytokines and the gut mucosal barrier. Dendritic cells activated by pathogens secrete several cytokines including IL-22 and IL-23. IL-23 stimulates several subsets of T cells (Th17 cells, γδ T cells, NK, and NK-T cells) to secrete IL-17 and IL-22. T cells promote amplification of the host response by stimulating the intestinal epithelium to secrete CXC chemokines (neutrophil chemoattractants) and antimicrobial peptides (lipocalin-2, calprotectin, Reg3γ, and β-defensins). While the Th17 response prevents bacterial dissemination from the gut, it also promotes colonization of the mucosa by pathogens that are resistant to some of the induced antimicrobial responses. The ability to acquire nutrients and associate with the expanded mucous layer during inflammation promotes colonization of pathogenic microbes