Interleukin-17 in pulmonary host defense

Interleukin (IL)-17A and IL-17F are produced by a novel class of effector alphabeta T cells called Th17 cells as well as gammadelta T cells. alphabeta IL-17-producing T cells are controlled by the transcription factor RORgammat and develop independent of GATA-3, T-bet, Stat 4, and Stat 6. Effector molecules produced by these cells include IL-17A, IL-17F, and IL-22. IL-17A and IL-17F bind to IL-17 receptor (IL-17R) and receptor signaling is critical for host defense against extracellular bacteria by regulating chemokine gradients for neutrophil emigration into infected tissue sites as well as via regulation of host granulopoiesis. Furthermore, it has recently been shown that IL-17 and IL-22 regulate the production of antimicrobial proteins in epithelium. Although Th17 cells are important in mucosal host defense, in the setting of retained antigenic stimulation, such as in the setting of asthma or chronic infection, such as in cystic fibrosis, or in the setting of autoimmunity, these cells can mediate immunopathology.