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

作者：Xie, Xiaoli; Mu, Lili; Yao, Xiuhua; Li, Na; Sun, Bo; Li, Ying; Zhan, Xiaoxia; Wang, Xinyue; Kang, Xiaoying; Wang, Jinghua; Liu, Yumei; Zhang, Yao; Wang, Guangyou; Wang, Dandan; Liu, Xijun; Kong, Qingfei^*; Li, Hulun

来源：Clinical Immunology, 2013, 148(2): 162-176.

DOI：10.1016/j.clim.2013.05.009

• All-trans retinoic acid
• Experimental autoimmune myasthenia gravis
• Germinal centers
• Follicular helper T cells
• Follicular regulatory T cells

All-trans retinoic acid (ATM) is a vitamin A metabolite with diverse immunomodulatory actions used therapeutically in the treatment of some autoimmune diseases. However, the effects that ATM may have on diminishing myasthenia gravis (MG) symptoms remain undefined. This study investigated the effect of ATM on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. Data presented in this study demonstrated that intraperitoneal injection of ATM 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(+)COS(median)) and that the Tfh:Tfr ratio was altered following ATM administration. In addition, ATM treatment restored the Th1/Th2/Th17/Treg balance. In vitro, ATM inhibited AChR-specific cell proliferation and eliciting apoptosis in these cells without affecting the cell cycle. ATM 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 ATM reduced EAMG severity by regulating Th cell profiles thereby providing new insights into the development of novel MG (or related) therapies.

• 出版日期2013-8
• 单位哈尔滨医科大学