Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Life Sci Alliance. 2020 Dec 4;4(1). doi: 10.26508/lsa.202000907. Print 2021 Jan.
Tertiary lymphoid structures (TLS) are organized aggregates of B and T cells formed ectopically during different stages of life in response to inflammation, infection, or cancer. Here, we describe formation of structures reminiscent of TLS in the spinal cord meninges under several central nervous system (CNS) pathologies. After acute spinal cord injury, B and T lymphocytes locally aggregate within the meninges to form TLS-like structures, and continue to accumulate during the late phase of the response to the injury, 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 special immune response develops in the meninges during various neurological pathologies in the CNS, a possible reflection of its immune privileged nature.
三级淋巴结构（TLS）是在生命的不同阶段，针对炎症、感染或癌症，异位形成的 B 细胞和 T 细胞的聚集物。在这里，我们描述了在几种中枢神经系统（CNS）疾病中，脊髓脑膜中形成类似于 TLS 的结构。在急性脊髓损伤后，B 和 T 淋巴细胞在脑膜内局部聚集形成 TLS 样结构，并在损伤反应的晚期继续积累，对随后的病理状况（如实验性自身免疫性脑脊髓炎）产生负面影响。使用慢性脊髓病理模型，肌萎缩侧索硬化症的 mSOD1 小鼠模型，我们通过单细胞 RNA 测序进一步表明，脑膜中的淋巴细胞龛形成，具有独特的组织和激活状态，包括前 B 细胞在脊髓脑膜中的积累。在 CNS 引流的颈淋巴结中未发现这种反应。目前的研究结果表明，在 CNS 中的各种神经病理学中，脑膜中会出现特殊的免疫反应，这可能反映了其免疫特权性质。
