The role of Th17 cytokines in primary mucosal immunity

Abstract

The T helper type 17 (Th17) lineage of CD4+ T-cells produce several effector molecules including IL-17A, IL-17F, IL-21, and IL-22. In addition to CD4+, αβ T-cells, these cytokines can be produced by natural killer and γδ T-cells. These effector cytokines can be produced rapidly upon infection at mucosal sites and evidence to date strongly implicates that this arm of the immune system plays a critical role in mucosal immunity to many extracellular pathogens. Moreover these cytokines can also coordinate adaptive immunity to some intracellular pathogens. In this review, we will highlight recent progress in our understanding of these cytokines, and mechanisms of their effector function in the mucosa.

Figure 1. Schema of Th17 effector in mucosal immunity

IL-17 and IL-22 can be produced by several immune cells including αβ, and γβT-cells, as well as NK cells. Receptors for IL-17a, IL-17F, and IL-22 are expressed on mucosal epithelial cells. Stimulation of epithelial cells with IL-17 and IL-22 induces G-CSF and CXC chemokine production. The combination of G-CSF and CXC chemokines such as CXCL1, CCXL2, CXCL5 and CXCL8 result in neutrophil recruitment required for bacterial and fungal clearance at mucosal sites. IL-22 and IL-17 can also augment the expression of antimicrobial peptides. IL-22, in part via the activation of STAT3 can also mediate epithelial repair which is critical to control of extracellular bacterial pathogens. In the setting of intracellular pathogens IL-17 can induce the production of IL-12 in DCs and drive Th1 immunity and intracellular bacterial control.