Bone marrow hematopoiesis drives multiple sclerosis progression

作者：Kaibin Shi, Handong Li, Ting Chang, Wenyan He, Ying Kong, Caiyun Qi, Ran Li, Huachen Huang, Zhibao Zhu, Pei Zheng, Zhe Ruan, Jie Zhou, Fu‐Dong Shi, Qiang Liu · 发表于：Cell · 年份：2022 · DOI：10.1016/j.cell.2022.05.020 · 被引用次数：170 · 研究领域：Immune cells in cancer、Hematopoietic Stem Cell Transplantation、Immunotherapy and Immune Responses

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.