Th17 cells and mucosal host defense

Abstract

Th17 cells are a new lineage of T-cells that are controlled by the transcription factor RORgammat and develop independent of GATA-3, T-bet, Stat 4 and Stat 6. Novel effector molecules produced by these cells include IL-17A, IL-17F, IL-22, and IL-26. IL-17RA binds IL-17A and IL-17F and is critical for host defense against extracellular planktonic bacteria by regulating chemokine gradients for neutrophil emigration into infected tissue sites as well as host granulopoiesis. Moreover, IL-17 and IL-22 regulate the production of antimicrobial proteins in mucosal epithelium. Although TGF-beta1 and IL-6 have been shown to be critical for development of Th17 cells from naive precursors, IL-23 is also important in regulating IL-17 release in mucosal tissues in response to infectious stimuli. Compared to Th1 cells, IL-23 and IL-17 show limited roles in controlling host defense against primary infections with intracellular bacteria such as Mycobacterium tuberculosis suggesting a predominate role of the Th17 lineage in host defense against extracellular pathogens. However, in the setting of chronic biofilm infections, as that occurs with cystic fibrosis or bronchiectasis, Th17 cells may be key contributors of tissue injury.