Muls Nathalie, Dang Hong Anh, Sindic Christian J M, van Pesch Vincent
Neurochemistry Unit, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
Neurochemistry Unit, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium; Cliniques Universitaires Saint-Luc, Brussels, Belgium.
PLoS One. 2014 Nov 20;9(11):e113025. doi: 10.1371/journal.pone.0113025. eCollection 2014.
Multiple sclerosis (MS) likely results from an imbalance between regulatory and inflammatory immune processes. CD39 is an ectoenzyme that cleaves ATP to AMP and has been suggested as a novel regulatory T cells (Treg) marker. As ATP has numerous proinflammatory effects, its degradation by CD39 has anti-inflammatory influence. The purpose of this study was to explore regulatory and inflammatory mechanisms activated in fingolimod treated MS patients.
Peripheral blood mononuclear cells (PBMCs) were isolated from relapsing-remitting MS patients before starting fingolimod and three months after therapy start. mRNA expression was assessed in ex vivo PBMCs. The proportions of CD8, B cells, CD4 and CD39-expressing cells were analysed by flow cytometry. Treg proportion was quantified by flow cytometry and methylation-specific qPCR. Fingolimod treatment increased mRNA levels of CD39, AHR and CYP1B1 but decreased mRNA expression of IL-17, IL-22 and FOXP3 mRNA in PBMCs. B cells, CD4+ cells and Treg proportions were significantly reduced by this treatment, but remaining CD4+ T cells were enriched in FOXP3+ cells and in CD39-expressing Tregs.
In addition to the decrease in circulating CD4+ T cells and CD19+ B cells, our findings highlight additional immunoregulatory mechanisms induced by fingolimod.
多发性硬化症（MS）可能是由调节性免疫过程与炎症性免疫过程之间的失衡所致。CD39是一种将ATP裂解为AMP的胞外酶，已被认为是一种新型调节性T细胞（Treg）标志物。由于ATP具有多种促炎作用，其被CD39降解具有抗炎影响。本研究的目的是探索在接受芬戈莫德治疗的MS患者中激活的调节和炎症机制。
从复发缓解型MS患者开始使用芬戈莫德之前以及治疗开始三个月后分离外周血单个核细胞（PBMC）。在体外PBMC中评估mRNA表达。通过流式细胞术分析表达CD8、B细胞、CD4和CD39的细胞比例。通过流式细胞术和甲基化特异性定量PCR对Treg比例进行定量。芬戈莫德治疗可增加PBMC中CD39、AHR和CYP1B1的mRNA水平，但降低IL-17、IL-22和FOXP3 mRNA的表达。该治疗可显著降低B细胞、CD4+细胞和Treg比例，但剩余的CD4+ T细胞中FOXP3+细胞和表达CD39的Treg富集。
除了循环CD4+ T细胞和CD19+ B细胞减少外，我们的研究结果还突出了芬戈莫德诱导的其他免疫调节机制。
