The Immunomodulatory Effects of All-trans Retinoic Acid on AChR-specific Lymphocytes / 现代生物医学进展

ABSTRACT

Objective:To observe the effects of All-trans retinoic acid (ATRA) on the immune functions of AChR-specific lymphcytes via in vitro assays,and investigate the possibility of ATRA in the clinical treatment of myasthenia gravis (MG).Methods:CFA control group and EAMG experimental rats were established to obtain single lymphocytes suspension and cells were followed by AChR97-116 peptide with or without ATRA stimulation for 72 h,and then viable cell population,cell apoptosis,cell cycle and the distribution of Th cells were determined by flow cytometry.CCK-8 assay was selected to evaluate the effects of ATRA on proliferatory ability of lymphocytes.ELISA was used to detect the antibody secretion of B cells affected by ATRA.Results:Compared with CFA group,lymphocytes obtained from EAMG rats had higher ratios of living cells,and this ratio was obviously decreased after ATRA treatment,P＜0.001.Different concentrations of ATRA promoted the apoptosis of AChR-specific cells (P＜0.001),and the promoted effects were ATRA dose-dependent,however,cell cycles were not changed.ATRA markedly inhibited the proliferation of cells from both CFA and EAMG groups,moreover,AChR-specific cells were more sensitive to ATRA treatment (P＜0.01) than that of cells from CFA rats (P＜0.05).The ratio of AChR-specific CD4+T cells was reduced by ATRA (P＜0.01),and ATRA incubation significantly promoted the percentages of Th2,(PCD4+-4IL-4+＜0.001),Treg (PCD4+-Foxp3+＜0.001) cell types,but markedly inhibited the percentages ofThl7 (PCD4+-IL-17+＜0.05),Thl (PCD4+-IFN-γ+＜0.001) cells.ELISA data showed us that ATRA obviously down regulated the antibody secretion of AChR-specific B cells,P＜0.01.Conclusions:ATRA not only inhibited the functions of AChR-specific T cells,but also suppressed the roles of AChR-specific B cells,predicating a therapeutic effect of ATRA on myasthenia gravis therapy.