Abstract
Epithelial cells are the first line of defense against external dangers, and contribute to induction of adaptive immunity including Th17 responses. However, it is unclear whether specific epithelial signaling pathways are essential for the development of robust IL-17–mediated immune responses. In mice, the development of psoriatic inflammation induced by imiquimod required keratinocyte TRAF6. Conditional deletion of TRAF6 in keratinocytes abrogated dendritic cell activation, IL-23 production, and IL-17 production by γδ T cells at the imiquimod-treated sites. In contrast, hapten-induced contact hypersensitivity and papain-induced IgE production were not affected by loss of TRAF6. Loss of psoriatic inflammation was not solely due to defective imiquimod sensing, as subcutaneous administration of IL-23 restored IL-17 production but did not reconstitute psoriatic pathology in the mutant animals. Thus, TRAF6 was required for the full development of IL-17–mediated inflammation. Therefore, epithelial TRAF6 signaling plays an essential role in both triggering and propagating IL-17–mediated psoriatic inflammation.
Authors
Reiko Matsumoto, Teruki Dainichi, Soken Tsuchiya, Takashi Nomura, Akihiko Kitoh, Matthew S. Hayden, Ken J. Ishii, Mayuri Tanaka, Tetsuya Honda, Gyohei Egawa, Atsushi Otsuka, Saeko Nakajima, Kenji Sakurai, Yuri Nakano, Takashi Kobayashi, Yukihiko Sugimoto, Kenji Kabashima
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