Multiple sclerosis (MS) therapeutic goals have traditionally been dichotomized into two distinct avenues: immune-modulatory-centric interventions and pro-regenerative strategies. Oligodendrocyte progenitor cells (OPCs) were regarded for many years solely in concern to their potential to generate oligodendrocytes and myelin in the central nervous system (CNS). However, accumulating data elucidate the multifaceted roles of OPCs, including their immunomodulatory functions, positioning them as cardinal constituents of the CNS’s immune landscape. In this review, we will discuss how the two therapeutic approaches converge. We present a model by which (1) an inflammation is required for the appropriate pro-myelinating immune function of OPCs in the chronically inflamed CNS, and (2) the immune function of OPCs is crucial for their ability to differentiate and promote remyelination. This model highlights the reciprocal interactions between OPCs’ pro-myelinating and immune-modulating functions. Additionally, we review the specific effects of anti- and pro-inflammatory interventions on OPCs, suggesting that immunosuppression adversely affects OPCs’ differentiation and immune functions. We suggest a multi-systemic therapeutic approach, which necessitates not a unidimensional focus but a harmonious balance between OPCs’ pro-myelinating and immune-modulatory functions.

中文翻译：

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炎症和髓鞘再生的相互作用：重新思考多发性硬化症治疗，重点关注少突胶质细胞祖细胞


多发性硬化症 (MS) 的治疗目标传统上分为两种不同的途径：以免疫调节为中心的干预措施和促再生策略。多年来，少突胶质细胞祖细胞 (OPC) 一直被人们所关注，只是因为它们在中枢神经系统 (CNS) 中产生少突胶质细胞和髓鞘质的潜力。然而，不断积累的数据阐明了 OPC 的多方面作用，包括其免疫调节功能，将其定位为中枢神经系统免疫景观的主要组成部分。在这篇综述中，我们将讨论这两种治疗方法如何融合。我们提出了一个模型，其中（1）慢性炎症中枢神经系统中 OPC 的适当促髓鞘形成免疫功能需要炎症，以及（2）OPC 的免疫功能对其分化和促进髓鞘再生的能力至关重要。该模型强调了 OPC 的促髓鞘形成和免疫调节功能之间的相互作用。此外，我们回顾了抗炎和促炎干预措施对 OPC 的具体影响，表明免疫抑制会对 OPC 的分化和免疫功能产生不利影响。我们建议采用多系统治疗方法，该方法不需要单一维度的关注，而是需要 OPC 的促髓鞘形成和免疫调节功能之间的和谐平衡。