Macrophages: a double-edged sword in experimental autoimmune encephalomyelitis.

Macrophages: a double-edged sword in experimental autoimmune encephalomyelitis.
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DOI:
10.1016/j.imlet.2014.03.006
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发表时间:
2014-07
期刊:
影响因子:
4.4
通讯作者:
Zhang GX
Zhang GX
中科院分区:
医学3区
文献类型:
--
作者:
Jiang Z;Jiang JX;Zhang GX

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多发性硬化症(MS)是中枢神经系统(CNS)的衰弱性神经系统疾病,其特征在于白细胞和树突状细胞的活化和浸润到CNS中。在MS及其动物模型(实验性自身免疫性脑脊髓炎(EAE))的初始阶段,外周巨噬细胞浸润到CNS中,在CNS中,它们与驻留的小胶质细胞一起参与疾病的诱导和发展。在早期阶段,小胶质细胞/巨噬细胞立即被激活成为经典激活的巨噬细胞(M1细胞),释放促炎细胞因子并损伤CNS组织。在后期,发炎CNS中的小胶质细胞/巨噬细胞活化较少,表现为交替活化的巨噬细胞表型(M2细胞),释放抗炎细胞因子,伴随炎症消退和组织修复。CNS中M1细胞和M2细胞的活化和极化之间的平衡对于疾病进展很重要。促炎性IFN-[H9253]和IL-12驱动M1细胞极化,而IL-4和IL-13驱动M2细胞极化。鉴于极化的巨噬细胞在明确的细胞因子环境中是可逆的,CNS中的巨噬细胞表型可以通过分子干预来调节。本文综述了小胶质细胞和巨噬细胞在中枢神经系统中的有害和有益作用,重点是M2细胞在EAE和MS患者中的作用。
Multiple sclerosis (MS) is a debilitating neurological disorder of the central nervous system (CNS), characterized by activation and infiltration of leukocytes and dendritic cells into the CNS. In the initial phase of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), peripheral macrophages infiltrate into the CNS, where, together with residential microglia, they participate in the induction and development of disease. During the early phase, microglia/macrophages are immediately activated to become classically activated macrophages (M1 cells), release pro-inflammatory cytokines and damage CNS tissue. During the later phase, microglia/macrophages in the inflamed CNS are less activated, present as alternatively activated macrophage phenotype (M2 cells), releasing anti-inflammatory cytokines, accompanied by inflammation resolution and tissue repair. The balance between activation and polarization of M1 cells and M2 cells in the CNS is important for disease progression. Pro-inflammatory IFN-[H9253] and IL-12 drive M1 cell polarization, while IL-4 and IL-13 drive M2 cell polarization. Given that polarized macrophages are reversible in a well-defined cytokine environment, macrophage phenotypes in the CNS can be modulated by molecular intervention. This review summarizes the detrimental and beneficial roles of microglia and macrophages in the CNS, with an emphasis on the role of M2 cells in EAE and MS patients.
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