title: Therapeutic effect of ergotope peptides on CIA by down-regulation of inflammatory and Th1/Th17 responses and induction of regulatory T cells.
abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease that results in a chronic and inflammatory disorder. Dynamic balance of helper T cells (Th)1, Th17 and regulatory T cells (Treg) is broken in RA. Since there is no cure for RA at present, it's necessary to find a truly effective and convenient treatment. Several studies intended to induce ergotopic regulation to treat autoimmune diseases. This study was undertaken to find the potential ergotope peptides and investigate its effect in treating the animal model of RA and their underlying regulatory mechanisms. Firstly, we selected the functional ergotope peptides from 25 overlapping peptides derived from interlukin(IL)-2 receptor (IL-2R) α chain, and then used these peptides to treat collagen-induced arthritis (CIA). The study showed ergotope peptides as immunomodulatory factors with great benefits at the clinical and pathologic levels. This effect was associated with the inhibition of type II collagen (CII)-specific proliferation and autoantibody production as well as the induction of anti-ergotypic immune response, the down-regulation of both Th1 and Th17 cells and their related components, and the emergence of Treg cells that had suppressive actions on autoreactive T cells. We also proved that cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and IL-10 are two important mediators which are critical to Treg suppressive function. The inhibition of Th1 and Th17 in established CIA could be attributed to ergotope induced Treg cells. Our findings reveal that ergotope peptides induce regulatory immune responses and restore immune tolerance, suggesting ergotope peptides treatment appears to be a novel approach to the therapy of RA patients and has a good application prospect with cheap, effective, convenient, wide-spectrum features.
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.
authors: Xiaoyin
authors: X
authors: Niu
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.
authors: Shaohua
authors: S
authors: Deng
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.|Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors: Shan
authors: S
authors: Li
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.
authors: Yebin
authors: Y
authors: Xi
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.|Guanghua Rheumatology Hospital, Shanghai, China. 540 Xinhua Road, Shanghai 200052, China.
authors: Chengzhen
authors: C
authors: Li
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.
authors: Li
authors: L
authors: Wang
authors: Guanghua Rheumatology Hospital, Shanghai, China. 540 Xinhua Road, Shanghai 200052, China.
authors: Dongyi
authors: D
authors: He
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.
authors: Zhaojun
authors: Z
authors: Wang
authors: Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China. 280 South Chongqing Road, Shanghai 200025, China.
authors: Guangjie
authors: G
authors: Chen
keywords: Th1; Th17; Treg; collagen-induced arthritis (CIA); ergotope peptides