Retinoid ameliorates experimental autoimmune myositis, with modulation of Th cell differentiation and antibody production in vivo

Abstract

Objective. Polymyositis and dermatomyositis are chronic inflammatory muscle diseases. Retinoids are compounds that bind to the retinoic acid binding site of retinoic acid receptors and have biologic activities similar to those of vitamin A. Recent studies indicate that retinoids promote Th2 differentiation and suppress Th1 and Th17 differentiation in vitro. The present study was undertaken to examine the effects of a synthetic retinoid, Am80, on experimental autoimmune myositis as well as on Th phenotype development and antibody production.Methods. Experimental autoimmune myositis was induced in SJL/J mice by immunization with rabbit myosin. Am80 was administered orally once daily. Its effects were evaluated by measurement of the numbers of infiltrating inflammatory cells, production of inflammatory cytokines in muscle, production of Th-specific cytokines by myosin-stimulated splenic T cells, and production of antimyosin antibodies in serum.Results. In mice with experimental autoimmune myositis, orally administered Am80 significantly reduced the number of infiltrating inflammatory cells and the expression of tumor necrosis factor ␣ and interleukin-1␤ (IL-1␤) in muscle. Moreover, Am80 increased production of interferon-␥, IL-4, and IL-10, but not IL-17, by myosin-stimulated splenic T cells of mice with experimental autoimmune myositis, suggesting that it could enhance differentiation into Th1 and Th2, but not Th17, in vivo. Am80 also decreased serum levels of IgG2a and IgG2b antimyosin antibodies, but did not affect levels of IgG1 antimyosin antibodies. In addition, it suppressed chemokine expression and activator protein 1 activity in myoblasts in vitro. Conclusion. The synthetic retinoid Am80 has an inhibitory effect on experimental autoimmune myositis. It might regulate the development of Th phenotype and antibody production in vivo, in addition to its effects on cytokine and chemokine production.

Acitretin exerted a greater influence on T‐helper (Th)1 and Th17 than on Th2 cells in treatment of psoriasis vulgaris

“…In our investigation, we found that acitretin could reverse Th17 preponderance in PV. Many researches have found retinoids could suppress Th17 in a number of autoimmune diseases, such as autoimmune myositis, allergic asthma and multiple sclerosis . Mucida et al .…”

Synthetic Retinoid AM80 Ameliorates Lung and Arthritic Autoimmune Responses by Inhibiting T Follicular Helper and Th17 Cell Responses

“…AM80 is a synthetic retinoic acid that is characterized by higher stability and fewer potential adverse effects compared to all-trans retinoic acid, one of the most active physiological members of the retinoid metabolites (16, 17). It has been reported that retinoic acid and AM80 ameliorate many autoimmune responses including experimental autoimmune myositis, experimental autoimmune encephalitis, and collagen-induced arthritis (18–21). As for retinoic acid’s effects in the lung, retinoic acid treatment has been shown to abrogate pulmonary emphysema (22, 23), but little is known about its effect in autoimmune-related lung diseases.…”

IL-4 and Retinoic Acid Synergistically Induce Regulatory Dendritic Cells Expressing Aldh1a2

“…Mechanistically, RA was shown to enhance TGF-β-induced Smad3 expression and phosphorylation, and to reduce the expression of IL-6 receptor α, IRF-4, and IL-23 receptor in T cells (26). In vivo , RA treatment suppresses Th1 and Th17-mediated immunopathology in various autoimmune disease models, including EAE (27–29), uveoretinitis (30), myositis (31), colitis (32–34), rheumatoid arthritis (35) and type-1 diabetes (36, 37). …”