Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies. Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies

Tertiary lymphoid structures (TLS) are organized aggregates of B and T cells formed ectopically during different life periods in response to inflammation, infection, or cancer. Here, we describe formation of structures reminiscence of TLS in the spinal cord meninges under several central nervous system (CNS) pathologies. Following acute spinal cord injury, B and T lymphocytes locally aggregate within the meninges to form TLS, which continue to accumulate during the late phase of repair, with a negative impact on subsequent pathological conditions, such as experimental autoimmune encephalomyelitis. Using a chronic model of spinal cord pathology, the mSOD1 mouse model of amyotrophic lateral sclerosis, we further showed by single cell RNA-sequencing that a meningeal lymphocyte niche forms, with a unique organization and activation state, including accumulation of pre-B cells in the spinal cord meninges. Such a response was not found in the CNS-draining cervical lymph nodes. The present findings suggest that a unique immune response develops in the meninges during various neurological pathologies in the CNS, a reflection of its immune privileged nature. Overall design: single cell RNA-seq of B and T cells from mSOD1 mouse meninges or lymph node

三级淋巴结构（tertiary lymphoid structures, TLS）是在不同生命阶段，因炎症、感染或癌症等因素异位形成的B细胞与T细胞有序聚集体。本研究报道了在多种中枢神经系统（central nervous system, CNS）病理状态下，脊髓脑膜中形成类似三级淋巴结构的聚集体。在急性脊髓损伤后，B淋巴细胞与T淋巴细胞会在脑膜局部聚集形成三级淋巴结构，该结构会在修复后期持续积累，并对后续的病理状态（如实验性自身免疫性脑脊髓炎）产生负面影响。本研究利用脊髓慢性病理模型——肌萎缩侧索硬化症（amyotrophic lateral sclerosis, ALS）的mSOD1小鼠模型，通过单细胞RNA测序（single cell RNA-sequencing）进一步证实，脑膜中会形成具有独特组织结构与激活状态的淋巴细胞微生态位，其中包括脊髓脑膜中前B细胞的聚集。而在中枢神经系统引流的颈部淋巴结中并未观察到此类免疫反应。本研究结果提示，在中枢神经系统的多种神经病理过程中，脑膜中会形成独特的免疫反应，这也反映了中枢神经系统的免疫豁免特性。实验设计：取自mSOD1小鼠脑膜或淋巴结的B细胞与T细胞的单细胞RNA测序