| First Author | Kiss MG | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 7 | Pages | 1502-1514.e8 |
| PubMed ID | 37160117 | Mgi Jnum | J:355198 |
| Mgi Id | MGI:7737846 | Doi | 10.1016/j.immuni.2023.04.013 |
| Citation | Kiss MG, et al. (2023) Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis. Immunity 56(7):1502-1514.e8 |
| abstractText | Glial cells and central nervous system (CNS)-infiltrating leukocytes contribute to multiple sclerosis (MS). However, the networks that govern crosstalk among these ontologically distinct populations remain unclear. Here, we show that, in mice and humans, CNS-resident astrocytes and infiltrating CD44(hi)CD4(+) T cells generated interleukin-3 (IL-3), while microglia and recruited myeloid cells expressed interleukin-3 receptor-a (IL-3Ra). Astrocytic and T cell IL-3 elicited an immune migratory and chemotactic program by IL-3Ra(+) myeloid cells that enhanced CNS immune cell infiltration, exacerbating MS and its preclinical model. Multiregional snRNA-seq of human CNS tissue revealed the appearance of IL3RA-expressing myeloid cells with chemotactic programming in MS plaques. IL3RA expression by plaque myeloid cells and IL-3 amount in the cerebrospinal fluid predicted myeloid and T cell abundance in the CNS and correlated with MS severity. Our findings establish IL-3:IL-3RA as a glial-peripheral immune network that prompts immune cell recruitment to the CNS and worsens MS. |
