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^high 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 T 细胞介导的中枢神经系统 (CNS) 自身免疫性疾病。骨髓造血干细胞和祖细胞 (HSPC) 可快速感知免疫激活，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 HSPC 偏向骨髓谱系，伴随着 MS 患者 T 细胞的克隆扩增。实验性自身免疫性脑脊髓炎（一种 MS 小鼠模型）的谱系追踪揭示了显着的骨髓造血功能，其中中性粒细胞和 Ly6C^{高输出增加}侵入中枢神经系统的单核细胞。我们发现髓鞘反应性 T 细胞以 CXCR4 依赖性方式优先迁移到骨髓隔室。这种异常的骨髓骨髓生成涉及 CCL5-CCR5 轴并增加 CNS 炎症和脱髓鞘。我们的研究表明，靶向骨髓生态位为治疗 MS 和其他自身免疫性疾病提供了一条途径。