Title:Role of IL-17F in the Pathogenesis of Psoriasis
Volume: 12
Issue: 2
Author(s): Masayuki Nakajima, Mio Kawaguchi, Hideaki Watanabe, Yuko Morishima, Shau-Ku Huang, Hiroaki Satoh and Nobuyuki Hizawa
Affiliation:
Keywords:
Psoriasis, IL-17 cytokine family, IL-17F.
Abstract: Psoriasis is a complex autoimmune inflammatory disease with a genetic basis. The increased
expression of IL-17F gene and protein is observed in the lesional skins of psoriatic patients. We and other
groups discovered human IL-17F gene that shows the highest homology with IL-17A. IL-17F induces
various inflammatory molecules, such as IL-6 and IL-8. IL-17F is mainly derived from Th17, Tc17 and
ILC3 cells, and induces CCL20 expression, resulting in the recruitment of additional IL-17F-producing
cells to enhance skin inflammation via CCR6. The receptor for IL-17F is the heterodimeric complex of
IL-17RA and IL-17RC, and several signaling pathways have been identified. Injection with IL-17F in
mice revealed marked neutrophilia in dermis, and its infiltration was significantly inhibited by anti-IL-8
antibody. Sequence variants of the IL-17F gene are associated with response to treatments, and a variant
(rs763780) of IL-17F encodes an antagonist for the wild-type IL-17F. Hence, IL-17F may play a pivotal
role in the pathogenesis of psoriasis, and may provide a promising therapeutic target for development of
novel strategies.
