多发性硬化三级淋巴结构的研究进展

Research progress of the tertiary lymphoid structure in multiple sclerosis

多发性硬化(multiple sclerosis,MS)是一种中枢神经系统自身免疫性疾病,其病理变化主要包括淋巴细胞浸润、胶质细胞活化、髓鞘脱失和神经退行变等。随着MS进展,外周浸润的免疫细胞通过释放C-X-C基序趋化因子配体(CXCL)13、CXCL12和肿瘤坏死因子α(TNF-α)等,诱导淋巴细胞集聚在脑脊膜或其覆盖的脑脊髓实质中,形成三级淋巴结构(TLS)。TLS可不依赖外周免疫系统发生强烈的免疫应答,产生致病性淋巴细胞,并持续活化其周围的小胶质细胞和星形胶质细胞,通过释放促炎性细胞因子和趋化因子,导致神经炎症加剧并导致MS症状持续和加重,甚至产生不可逆性的神经损伤,这些均与MS的慢性进展密切相关。我们就TLS在不同类型MS中的发生、分布以及组织结构等方面的研究进展进行综述,为慢性进展期MS的治疗提供新思路。

Multiple sclerosis(MS)is a chronic autoimmune disease of the central nervous system(CNS),which is characterized by infiltration of immune cells,glia activation,demyelination and neurodegeneration.With the progression of MS,the peripheric infiltrated immune cells promote lymphocytes to locate in parenchyma or meninges adjacent to active lesions by secreting cytokines,such as C-X-C motif chemokine ligand(CXCL)13,CXCL12 and tumor necrosis factor-α(TNF-α),contributing to the formation of tertiary lymphoid structure(TLS).TLS formation in the CNS can directly trigger immune reaction independent from peripheral immune system,leading to the differentiation of pathogenic lymphocytes,the activation of microglia and astrocyte,and the recruitment of additional peripheral immune cells into the CNS by secreting proinflammatory cytokines and chemokines.The immune reaction in CNS caused by TLS leads to aggravated neuroinflammation and pathological changes,even irreversible neuron damage,which is thought to be responsible the progression of MS.The formation,distribution,tissue structure,and the mechanism of formation and distribution of the TLS in MS are reviewed in this article,which may contribute to potential therapeutic approaches for chronic progressive MS.