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.


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.

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*