IL-17F: Regulation, signaling and function in inflammation

The IL-17 cytokine family is composed of six members. IL-17F, discovered in 2001, recently has drawn increasing attention due to its greatest similarity to IL-17, a widely recognized inflammatory cytokine. The genes encoding IL-17 and IL-17F are localized in the same chromosomal region and are co-expressed by CD4+ and γδ T cells. IL-17F can be secreted as homodimers or heterodimers with IL-17. Similar to IL-17, IL-17F utilizes IL-17RA and IL-17RC as its receptor and employs Act1 and TRAF6 as its signal transducers to induce the expression of pro-inflammatory cytokines and chemokines in many different cell types. However, mice lacking either IL-17 or IL-17F exhibit distinct defects in experimental models of asthma and colitis. These results have laid the basis to understand the role of IL-17F in the pathogenesis of human diseases.