Bone marrow hematopoiesis drives multiple sclerosis progression

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

doi:10.1016/j.cell.2022.05.020

Bone marrow hematopoiesis drives multiple sclerosis progression

Cell. 2022 Jun 23;185(13):2234-2247.e17. doi: 10.1016/j.cell.2022.05.020. Epub 2022 Jun 15.

Authors

Kaibin Shi¹, Handong Li², Ting Chang³, Wenyan He⁴, Ying Kong², Caiyun Qi², Ran Li², Huachen Huang², Zhibao Zhu⁵, Pei Zheng², Zhe Ruan³, Jie Zhou⁶, Fu-Dong Shi¹, Qiang Liu⁷

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 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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow
Encephalomyelitis, Autoimmune, Experimental*
Hematopoiesis
Humans
Mice
Mice, Inbred C57BL
Multiple Sclerosis*