ATRA alters humoral responses associated with amelioration of EAMG symptoms by balancing Tfh/Tfr helper cell profiles

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• 作者：Xiaoli Xie ; Lili Mu ; Xiuhua Yao ; Na Li ; Bo Sun ; Ying Li ; Xiaoxia Zhan ; Xinyue Wang ; Xiaoying Kang ; Jinghua Wang ; Yumei Liu ; Yao Zhang ; Guangyou Wang ; D ; an Wang ; Xijun Liu ; Qingfei Kong ; Hulun Li
• 关键词：ATRA ; all-trans retinoic acid ; RA ; retinoic acid ; MG ; myasthenia gravis ; EAMG ; experimental autoimmune myasthenia gravis ; AChR ; acetylcholine receptor ; R-AChR97&ndash ; 116 ; rat AChR ¦Á97&ndash ; 116 peptide ; GCs ; germinal centers ; Tfh ; follicular helper T ce
• 刊名：Clinical Immunology
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：148
• 期：2
• 页码：162-176
• 全文大小：2716 K

文摘

All-trans retinoic acid (ATRA) is a vitamin A metabolite with diverse immunomodulatory actions used therapeutically in the treatment of some autoimmune diseases. However, the effects that ATRA may have on diminishing myasthenia gravis (MG) symptoms remain undefined. This study investigated the effect of ATRA on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. Data presented in this study demonstrated that intraperitoneal injection of ATRA ameliorated EAMG pathology in rats associated with reduced total anti-acetylcholine receptor (AChR) serum IgG levels. We observed that EAMG development was accompanied by an increase in follicular helper T cells (Tfh, defined as CD4⁺CXCR5⁺ICOS^high) and a decrease of follicular regulatory T cells (Tfr, defined as CD4⁺Foxp3⁺CXCR5⁺ICOS^median) and that the Tfh:Tfr ratio was altered following ATRA administration. In addition, ATRA treatment restored the Th1/Th2/Th17/Treg balance. In vitro, ATRA inhibited AChR-specific cell proliferation and eliciting apoptosis in these cells without affecting the cell cycle. ATRA also altered the Th distribution in animals presenting with EAMG resulting in a reduction in Th1/Th17/Tfh cells and increasing the number of Th2/Treg/Tfr cell types. These results suggested that ATRA reduced EAMG severity by regulating Th cell profiles thereby providing new insights into the development of novel MG (or related) therapies.