CD30L/CD30 protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by Vγ4+ γδ T cells

Dan Yue; Yong You; Xiaoqing Zhang; Biao Wang; Xiao Wang; Ruiqun Qi; Fan Yang; Xin Meng; Yasunobu Yoshikai; Yuanyuan Wang; Xun Sun

doi:10.1016/j.jaut.2019.04.009

CD30L/CD30 protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by Vγ4⁺ γδ T cells

J Autoimmun. 2019 Jul:101:70-85. doi: 10.1016/j.jaut.2019.04.009. Epub 2019 Apr 18.

Authors

Dan Yue¹, Yong You², Xiaoqing Zhang², Biao Wang³, Xiao Wang², Ruiqun Qi⁴, Fan Yang⁵, Xin Meng³, Yasunobu Yoshikai⁶, Yuanyuan Wang⁷, Xun Sun⁸

Affiliations

¹ Department of Immunology, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China; Laboratory Medicine Department, Sheng Jing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, Liaoning Province, PR China; Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
² Department of Immunology, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China.
³ Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning Province, PR China.
⁴ Department of Dermatology, No.1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, Liaoning Province, PR China.
⁵ Department of Dermatology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, Liaoning Province, PR China.
⁶ Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
⁷ Department of Anesthesiology, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, PR China. Electronic address: shetao1220@hotmail.com.
⁸ Department of Immunology, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China. Electronic address: wsunxun1220@cmu.edu.cn.

PMID: 31005389
DOI: 10.1016/j.jaut.2019.04.009

Abstract

Psoriasis is a common, autoimmune, chronic inflammatory skin disease. It has been demonstrated that cutaneous T17 cells play an important pro-inflammatory role in the pathogenesis of psoriasis, through the production of various Th17-related cytokines. Our previous studies have demonstrated that CD30L/CD30 signal plays a pivotal role in the differentiation of CD4⁺ Th17 cells and Vγ6⁺γδ T17 cells in the gut-associated lymphoid tissues of mouse. However, its effect on the pathogenesis of psoriasis is unknown. Here, we fully prove that CD30L/CD30 signaling plays a novel protective role in the development of psoriasis in mice, through selective inhibition of CCR6 expression and Th17-related cytokine synthesis in the Vγ4⁺γδ T17 cell subset. Meanwhile, treatment with agonistic anti-CD30 mAb had a significant therapeutic effect on our psoriasis mouse model. Therefore, the CD30L/CD30 signaling pathway is an ideal target for antibody therapy, which may become a new approach for the immunobiological treatment of psoriasis.

Keywords: CCR6; CD30 ligand; IL-17A; Psoriasis; Vγ4(+) γδ T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Biopsy
CD30 Ligand / genetics
CD30 Ligand / metabolism*
Cell Movement / genetics
Cell Movement / immunology
Cytokines / biosynthesis*
Disease Susceptibility
Gene Deletion
Gene Expression
Immunophenotyping
Ki-1 Antigen / genetics
Ki-1 Antigen / metabolism*
Male
Mice
Psoriasis / etiology*
Psoriasis / metabolism*
Psoriasis / pathology
Receptors, Antigen, T-Cell, gamma-delta / metabolism*
Signal Transduction
Th17 Cells / immunology*
Th17 Cells / metabolism*

Substances

Biomarkers
CD30 Ligand
Cytokines
Ki-1 Antigen
Receptors, Antigen, T-Cell, gamma-delta