2. Academic Validation
  3. Bone marrow hematopoiesis drives multiple sclerosis progression

Bone marrow hematopoiesis drives multiple sclerosis progression

  • Cell. 2022 Jun 23;185(13):2234-2247.e17. doi: 10.1016/j.cell.2022.05.020.
Kaibin Shi 1,  Handong Li 2,  Ting Chang 3,  Wenyan He 4,  Ying Kong 2,  Caiyun Qi 2,  Ran Li 2,  Huachen Huang 2,  Zhibao Zhu 5,  Pei Zheng 2,  Zhe Ruan 3,  Jie Zhou 6,  Fu-Dong Shi 1,  Qiang Liu 7
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Neurology, Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 3 Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi 710038, China.
  • 4 Center for Neurological Diseases, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
  • 5 Department of Neurology, Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350005, China.
  • 6 Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
  • 7 Department of Neurology, Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: qliu@tmu.edu.cn.
PMID: 35709748 DOI: 10.1016/j.cell.2022.05.020
Abstract

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.

Keywords

autoreactive T cells; bone marrow; multiple sclerosis; myelopoiesis; neuroinflammation.

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