Department of Neurology, Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin 300052, China; Center for Neurological Diseases, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Department of Neurology, Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Cell. 2022 Jun 23;185(13):2234-2247.e17. doi: 10.1016/j.cell.2022.05.020. Epub 2022 Jun 15.
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients. Lineage tracing in experimental autoimmune encephalomyelitis, a mouse model of MS, reveals remarkable bone marrow myelopoiesis with an augmented output of neutrophils and Ly6C monocytes that invade the CNS. We found that myelin-reactive T cells preferentially migrate into the bone marrow compartment in a CXCR4-dependent manner. This aberrant bone marrow myelopoiesis involves the CCL5-CCR5 axis and augments CNS inflammation and demyelination. Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders.
多发性硬化症（MS）是一种中枢神经系统（CNS）的 T 细胞介导的自身免疫性疾病。骨髓造血干细胞和祖细胞（HSPCs）能迅速感知免疫激活，但它们与 MS 中自身反应性 T 细胞的潜在相互作用尚不清楚。在这里，我们报告骨髓 HSPCs 向髓系分化与 MS 患者 T 细胞的克隆扩增同时发生。实验性自身免疫性脑脊髓炎（EAE），MS 的小鼠模型中的谱系追踪显示骨髓中有显著的髓样细胞生成，中性粒细胞和 Ly6C 单核细胞的产量增加，这些细胞会侵入中枢神经系统。我们发现，髓鞘反应性 T 细胞优先以 CXCR4 依赖的方式迁移到骨髓腔中。这种异常的骨髓髓样细胞生成涉及 CCL5-CCR5 轴，并增强中枢神经系统炎症和脱髓鞘。我们的研究表明，靶向骨髓龛可能是治疗 MS 和其他自身免疫性疾病的一种途径。
