IL-17A and IL-17F are members of the IL-17 family and signature Th17 cytokines. Of the six IL-17 family members, IL-17F and IL-17A share the strongest homology (50% amino acid identity) and the two genes are located in the same chromosomal region. Although both IL-17A and IL- 17F were originally found to be produced as disulfide-linked homodimers, recent studies have confirmed the production of IL-17A/IL-17F heterodimers in in vitro-differentiated and polarized Th17 cells. Activated human CD4+ T cells in culture were found to secrete IL-17F homodimer at 10-fold higher levels than IL-17A homodimer, suggesting that the majority of the IL-17A protein expressed exists in the form of the IL-17AF heterodimer. Studies of Th17 polarized mouse splenocytes also indicate the majority of IL-17 made is the IL-17A/F heterodimer. IL-17F and IL-17A have been observed in tissue samples from various autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, and asthma.