Development of novel immunotherapies using retinoid X agonists

维甲酸（Retinoic acid， RA）通过与维甲酸受体（Retinoic acid receptor， RAR）结合，增强Foxp3+诱导调节性T细胞（iTreg） tgf - β依赖性分化，抑制Th17分化。目前尚不清楚rxr介导的刺激是否会影响iTreg和Th17的分化。我们在这里发现RXR激动剂增强了RA或RAR激动剂增强CD4+CD25- T细胞获得Foxp3表达和抑制功能的能力。单独使用RXR激动剂可抑制ror - γ -t mRNA和IL-17的表达。当RA浓度较低时，RXR激动剂与RA联合使用可抑制Th17的分化。因此，持续使用RXR激动剂治疗可改善实验性自身免疫性脑脊髓炎。这些结果表明，RXR刺激分别增强了Foxp3+ iTreg和Th17分化的rar依赖和独立调节。

Retinoic acid (RA) enhances TGF-beta-dependent differentiation of Foxp3+ inducible regulatory T cells (iTreg) and inhibits Th17 differentiation by binding to the retinoic acid receptor (RAR). It remained unclear if RXR-mediated stimulation affected the iTreg and Th17 differentiation. We found here that the RXR agonists augmented the ability of RA or the RAR agonist to enhance CD4+CD25- T cells to acquire Foxp3 expression and suppressive function.RXR agonists alone suppressed ROR-gamma-t mRNA and IL-17 expression. The combination of an RXR agonist and RA additively suppressed Th17 differentiation when the concentration of RA was low. Accordingly, continuous treatment with an RXR agonist ameliorated experimental autoimmune encephalomyelitis. These results suggest that RXR stimulation enhances RAR-dependent and independent modulation of Foxp3+ iTreg and Th17 differentiation, respectively.