Skuljec Jelena, Sardari Maryam, Su Chuanxin, Müller-Dahlke Julia, Singh Vikramjeet, Janjic Marija M, Kleinschnitz Christoph, Pul Refik
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, 45147 Essen, Germany.
Department of Neurology, Hannover Medical School, 30625 Hannover, Germany.
Int J Mol Sci. 2025 Mar 26;26(7):3013. doi: 10.3390/ijms26073013.
Glatiramer acetate (GA) is the first-line therapy for relapsing-remitting multiple sclerosis (MS) and is increasingly demonstrating promising therapeutic benefits in a range of other conditions. Despite its extensive use, the precise pharmacological mechanism of GA remains unclear. In addition to T and B cells, dendritic cells (DCs) and monocytes play significant roles in the neuroinflammation associated with MS, positioning them as potential initial targets for GA. Here, we investigated GA's influence on the differentiation of human monocytes from healthy donors into monocyte-derived dendritic cells (moDCs) and assessed their activation status. Our results indicate that GA treatment does not hinder the differentiation of monocytes into moDCs or macrophages. Notably, we observed a significant increase in the expression of molecules required for antigen recognition, presentation, and co-stimulation in GA-treated moDCs. Conversely, there was a significant downregulation of CD1a, which is crucial for activating auto-aggressive T cells that respond to the lipid components of myelin. Furthermore, GA treatment resulted in an increased expression of CD68 on both CD14CD16 and CD14CD16 monocyte subsets. These in vitro findings suggest that GA treatment does not impede the generation of moDCs under inflammatory conditions; however, it may modify their functional characteristics in potentially beneficial ways. This provides a basis for future clinical studies in MS patients to elucidate its precise mode of action.
醋酸格拉替雷(GA)是复发缓解型多发性硬化症(MS)的一线治疗药物,并且在一系列其他病症中越来越显示出有前景的治疗益处。尽管其被广泛使用,但GA的确切药理机制仍不清楚。除了T细胞和B细胞外,树突状细胞(DC)和单核细胞在与MS相关的神经炎症中起重要作用,这使它们成为GA潜在的初始靶点。在此,我们研究了GA对健康供体的人单核细胞分化为单核细胞衍生树突状细胞(moDC)的影响,并评估了它们的激活状态。我们的结果表明,GA处理不会阻碍单核细胞分化为moDC或巨噬细胞。值得注意的是,我们观察到GA处理的moDC中抗原识别、呈递和共刺激所需分子的表达显著增加。相反,对于激活对髓磷脂脂质成分产生反应的自身攻击性T细胞至关重要的CD1a显著下调。此外,GA处理导致CD14CD16和CD14CD16单核细胞亚群上CD68的表达增加。这些体外研究结果表明,GA处理在炎症条件下不会阻碍moDC的生成;然而,它可能以潜在有益的方式改变其功能特性。这为未来在MS患者中进行临床研究以阐明其确切作用方式提供了基础。