Epithelial TRAF6 drives IL-17–mediated psoriatic inflammation
| Autor: | Ken Ishii, Teruki Dainichi, Kenji Sakurai, Tetsuya Honda, Gyohei Egawa, Yukihiko Sugimoto, Reiko Matsumoto, Matthew S. Hayden, Mayuri Tanaka, Kenji Kabashima, Soken Tsuchiya, Akihiko Kitoh, Saeko Nakajima, Takashi Nomura, Atsushi Otsuka, Takashi Kobayashi, Yuri Nakano |
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| Rok vydání: | 2018 |
| Předmět: |
Keratinocytes
Male 0301 basic medicine Primary Cell Culture Inflammation Immunoglobulin E Mice 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Humans Psoriasis Intraepithelial Lymphocytes Cells Cultured Skin Mice Knockout TNF Receptor-Associated Factor 6 Imiquimod Receptors Interleukin-17 biology business.industry Interleukin-17 General Medicine Dendritic cell Acquired immune system Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cancer research biology.protein Female Interleukin 17 medicine.symptom Signal transduction Keratinocyte business Signal Transduction Research Article 030215 immunology |
| Zdroj: | JCI Insight. 3 |
| ISSN: | 2379-3708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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