The roles of IL-17C in T cell-dependent and -independent inflammatory diseases

• Published in: Scientific reports 2018-10, Vol.8 (1), p.15750-14, Article 15750
• Main Authors: Yamaguchi, Sachiko, Nambu, Aya, Numata, Takafumi, Yoshizaki, Takamichi, Narushima, Seiko, Shimura, Eri, Hiraishi, Yoshihisa, Arae, Ken, Morita, Hideaki, Matsumoto, Kenji, Hisatome, Ichiro, Sudo, Katsuko, Nakae, Susumu
• Format: Article
• Language: English
• Subjects: 13/21; 13/31; 631/250/127/1213; 631/250/256/2516; 64/60; Animal models; Bleomycin; Colitis; Colon; Concanavalin A; Contact dermatitis; Dermatitis; Dextran; Dinitrofluorobenzene; Endotoxin shock; Eosinophilia; Epithelial cells; Fibrosis; Hepatitis; Humanities and Social Sciences; Hypersensitivity; Imiquimod; Inflammatory bowel disease; Inflammatory diseases; Interleukin 1; Interleukin 17; Lipopolysaccharides; Lung diseases; Lymphocytes; Lymphocytes T; multidisciplinary; Neutrophilia; Psoriasis; Respiratory tract; Rodents; Science; Science (multidisciplinary); Skin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-34054-x

IL-17C, which is a member of the IL-17 family of cytokines, is preferentially produced by epithelial cells in the lung, skin and colon, suggesting that IL-17C may be involved in not only host defense but also inflammatory diseases in those tissues. In support of that, IL-17C was demonstrated to contribute to development of T cell-dependent imiquimod-induced psoriatic dermatitis and T cell-independent dextran sodium sulfate-induced acute colitis using mice deficient in IL-17C and/or IL-17RE, which is a component of the receptor for IL-17C. However, the roles of IL-17C in other inflammatory diseases remain poorly understood. Therefore, we investigated the contributions of IL-17C to development of certain disease models using Il17c −/− mice, which we newly generated. Those mice showed normal development of T cell-dependent inflammatory diseases such as FITC- and DNFB-induced contact dermatitis/contact hypersensitivity (CHS) and concanavalin A-induced hepatitis, and T cell-independent inflammatory diseases such as bleomycin-induced pulmonary fibrosis, papain-induced airway eosinophilia and LPS-induced airway neutrophilia. On the other hand, those mice were highly resistant to LPS-induced endotoxin shock, indicating that IL-17C is crucial for protection against that immunological reaction. Therefore, IL-17C neutralization may represent a novel therapeutic approach for sepsis, in addition to psoriasis and acute colitis.