Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis.
Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis.
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DOI：
10.3389/fnins.2015.00287
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发表时间：
2015
影响因子：
4.3
通讯作者：
Dittel BN
中科院分区：
文献类型：
--
作者：
Miller NM;Wang J;Tan Y;Dittel BN
多发性硬化症(MS)是一种中枢神经系统(CNS)自身免疫性疾病，由T辅助细胞(H)1和/或Th17 CD4T细胞介导，导致炎性病变发展、脱髓鞘和神经元损伤。免疫调节机制的缺陷被认为在MS的发病机制中发挥了作用，虽然早期的临床试验表明干扰素-γ对MS是有害的，但在实验性自身免疫性脑脊髓炎(MS)小鼠模型上的研究表明，干扰素-γ在中枢神经系统内表现出许多抗炎特性。这些机制包括抑制IL-17的产生、诱导调节性T细胞、T细胞的凋亡和调节趋化因子的产生。缺乏干扰素-γ或其受体的小鼠有助于破译干扰素-γ在中枢神经系统的抗炎特性。特别是，他们揭示了干扰素-γ是中性粒细胞重新聚集到中枢神经系统的主要调节因子，包括破坏血脑屏障和产生活性氧等多种机制被认为参与了EAE的发生和发展。中性粒细胞也被证明在EAE复发中起着重要作用。到目前为止，中性粒细胞还没有被认为是多发性硬化症的驱动因素，但最近在很大程度上基于强有力的EAE数据，该领域的一些研究人员正在重新评估这一观点。
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) mediated by T helper (h)1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE), indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB) and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on strong EAE data this view is being reevaluated by some investigators in the field.