Bone marrow hematopoiesis drives multiple sclerosis progression
×÷ÕߣºKaibinShi, HandongLi, TingChang ,WenyanHe , YingKong , CaiyunQi , RanLi , HuachenHuang , ZhibaoZhu , PeiZheng , ZheRuan , JieZhou , Fu-DongShi , QiangLiu£¨Department of Neurology, Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin 300052, China£©
·¢±íÇé¿ö£ºCell.2022 Jun 23;185(13):2234-2247.e17.
doi: 10.1016/j.cell.2022.05.020. Epub 2022 Jun 15.
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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 Ly6Chigh 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.
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