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

Sachiko Yamaguchi,Hideaki Morita,Aya Nambu,Eri Shimura,Ichiro Hisatome,Takamichi Yoshizaki,Susumu Nakae,Ken Arae,Seiko Narushima,Yoshihisa Hiraishi,Katsuko Sudo,Takafumi Numata,Kenji Matsumoto

doi:10.1038/s41598-018-34054-x

Abstract

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.

Highlights

IL-17C is a member of the IL-17 family of cytokines that includes IL-17A, IL-17B, IL-17D, IL-17E/IL-25 and IL-17F
IL-17C is thought to be involved in tumorigenesis: increased expression of Il17c mRNA and IL-17RE protein was observed in lung cancer and hepatocellular carcinoma, respectively[17,18], and tumor growth was reduced in Il17c-deficient (Il17c−/−) mice after non-typeable Haemophilus influenza infection[17] and in Il17re−/− mice on the Apcmin/+ background[19]
We investigated the roles of IL-17C in T cell-dependent diseases such as contact dermatitis and hepatitis, T cell-independent diseases such as pulmonary fibrosis and inflammation, and endotoxin shock using Il17c−/− mice, which we newly generated

Summary

Introduction

IL-17C is a member of the IL-17 family of cytokines that includes IL-17A, IL-17B, IL-17D, IL-17E/IL-25 and IL-17F. Inappropriate/excessive IL-17C expression may be involved in development or regulation of various disorders in mice and/or humans. Mice deficient in Il17c and Il17re showed aggravated inflammation during dextran sodium sulfate-induced colitis[3,4,16], suggesting that IL-17C plays a regulatory role www.nature.com/scientificreports/. IL-17C is thought to be involved in tumorigenesis: increased expression of Il17c mRNA and IL-17RE protein was observed in lung cancer and hepatocellular carcinoma, respectively[17,18], and tumor growth was reduced in Il17c-deficient (Il17c−/−) mice after non-typeable Haemophilus influenza infection[17] and in Il17re−/− mice on the Apcmin/+ background[19]. We investigated the roles of IL-17C in T cell-dependent diseases such as contact dermatitis and hepatitis, T cell-independent diseases such as pulmonary fibrosis and inflammation, and endotoxin shock using Il17c−/− mice, which we newly generated

Methods

Results

Conclusion