IL-17F belongs to the IL-17 cytokine family which includes IL-17A, B, C, D, and E (also called IL-25). IL-17F shares the strongest homology to IL-17A. They share 50% amino acid sequence homology.? Recently, an IL-17–IL-17F heterodimer was found to be expressed in Th17 cells together with IL-17 and IL-17F homodimers. IL-17 and IL-17F gene promoters share the same pattern of chromatin remodeling in differentiated Th17 cells. T cell populations in vitro and in vivo have shown different ratios of IL-17 and IL-17F expression. IL-17, IL-17F regulates proinflammatory gene expression in vitro. Studies in vivo using Il17a(-/-), Il17f(-/-), and Il17a(-/-)Il17f(-/-) mice showed that IL-17F played only marginal roles, if at all, in the development of delayed-type and contact hypersensitivities, autoimmune encephalomyelitis, collagen-induced arthritis, and arthritis in Il1rn(-/-) mice. In contrast, both IL-17F and IL-17A were involved in host defense against mucoepithelial infection by Staphylococcus aureus and Citrobacter rodentium. Additional studies in vivo have suggested a role for IL-17F in the induction of neutrophilia in the lungs and in the exacerbation of Ag-induced pulmonary inflammation.