| First Author | Paré A | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 6 | Pages | E1194-E1203 |
| PubMed ID | 29358392 | Mgi Jnum | J:319453 |
| Mgi Id | MGI:6863502 | Doi | 10.1073/pnas.1714948115 |
| Citation | Pare A, et al. (2018) IL-1beta enables CNS access to CCR2(hi) monocytes and the generation of pathogenic cells through GM-CSF released by CNS endothelial cells. Proc Natl Acad Sci U S A 115(6):E1194-E1203 |
| abstractText | Molecular interventions that limit pathogenic CNS inflammation are used to treat autoimmune conditions such as multiple sclerosis (MS). Remarkably, IL-1beta-knockout mice are highly resistant to experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we show that interfering with the IL-1beta/IL-1R1 axis severely impairs the transmigration of myeloid cells across central nervous system (CNS) endothelial cells (ECs). Notably, we report that IL-1beta expression by inflammatory CCR2(hi) monocytes favors their entry into the spinal cord before EAE onset. Following activation with IL-1beta, CNS ECs release GM-CSF, which in turn converts monocytes into antigen-presenting cells (APCs). Accordingly, spinal cord-infiltrated monocyte-derived APCs are associated with dividing CD4(+) T cells. Factors released from the interaction between IL-1beta-competent myeloid cells and CD4(+) T cells are highly toxic to neurons. Together, our results suggest that IL-1beta signaling is an entry point for targeting both the initiation and exacerbation of neuroinflammation. |
