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.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease of polyarticular arthritis affecting approximately 1% of adults worldwide [1,2]
Our study found that a potentially beneficial immunomodulatory response toward activated T cells in general, against peptides derived from the IL-2Rα-chain, was obtained by vaccinating RA patients with expanded, activated and irradiated autologous synovial T cells [21]
We found that T cell vaccination (TCV) vaccine could induce antiergotypic regulation in patients with RA and in mice with collagen-induced arthritis (CIA) [21]
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease of polyarticular arthritis affecting approximately 1% of adults worldwide [1,2]. The etiology and pathogenesis of RA remain unknown, immunological hyperreactivity caused by many T cells, mostly cluster of differentiation (CD) 4 and plasma cells, is generally considered to be an important contributor to its development. Both clinical and experimental evidence strongly suggest that helper T cell (Th) 1 responses and the principal effector cytokine interferon (IFN)-γ mediate the synovial inflammatory cascade, synovial hyperplasia and joint destruction in arthritis [3,4,5,6]. Th1, Th17 and Treg may remain in dynamic
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