| First Author | Shi K | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 13 | Pages | 2234-2247.e17 |
| PubMed ID | 35709748 | Mgi Jnum | J:351499 |
| Mgi Id | MGI:7295267 | Doi | 10.1016/j.cell.2022.05.020 |
| Citation | Shi K, et al. (2022) Bone marrow hematopoiesis drives multiple sclerosis progression. Cell 185(13):2234-2247.e17 |
| abstractText | 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. |
