Dendritic cell-targeted CD40 DNA vaccine suppresses Th17 and ameliorates progression of experimental autoimmune glomerulonephritis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Qing Li¹  Qi Cao¹  Chengshi Wang¹  Hanh Nguyen¹  Xin Maggie Wang¹  Guoping Zheng¹  Yuan Min Wang⁴  Shilian Hu⁵  Stephen I. Alexander⁴  David C.H. Harris¹  Yiping Wang¹ 

[1] Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney;The Central Laboratory of Medical Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China;Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University;Centre for Kidney Research, Children's Hospital at Westmead, University of Sydney;Anhui Geriatrics Institute, Department of Geriatrics, Anhui Provincial Hospital, Anhui Medical University

关键词: Experimental autoimmune glomerulonephritis (EAG);    DNA vaccination;    CD40;    Dendritic cells;    DEC205;    Th17 cells;   

DOI  :  10.1002/JLB.5A0818-333R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The CD40-CD40L costimulatory pathway is critical for T cell activation in autoimmune disease. We have previously found that blocking the CD40-CD40L pathway using a dendritic cell-targeted CD40 DNA (DEC-CD40) vaccine prevented the development of Heymann nephritis. In this study, we explored the effect of a DEC-CD40 vaccine in the treatment of experimental autoimmune glomerulonephritis (EAG), an animal model of human Goodpasture’s disease induced by antigen ?3IV-NC1. DEC-CD40 vaccine given at week 3 and week 6 after 3IV-NC1 injection reduced kidney structural and functional injury significantly in EAG. DEC-CD40 vaccination suppressed Th17 cell numbers and Th17 immune responses in kidney and spleen, but did not alter Th1 cells number and responses. Serum derived from rats with DEC-CD40 vaccination suppressed Th17 differentiation, but not Th1 differentiation in vitro. Furthermore, B cell activation, driven by Th17 cytokines, was suppressed by serum from rats vaccinated with DEC-CD40. A DNA vaccine encoding CD40 and targeting dendritic cell, ameliorates kidney injury in both early and late stages in EAG rats, indicating DEC-CD40 vaccination has a therapeutic role in EAG. Its effect is associated with the reduction of Th17 differentiation and Th17-mediated B cell activation.

【 授权许可】

CC BY