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
  • 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: [email protected].
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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