| First Author | Lévesque SA | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 6 | Pages | 929-49 |
| PubMed ID | 27139491 | Mgi Jnum | J:234784 |
| Mgi Id | MGI:5790879 | Doi | 10.1084/jem.20151437 |
| Citation | Levesque SA, et al. (2016) Myeloid cell transmigration across the CNS vasculature triggers IL-1beta-driven neuroinflammation during autoimmune encephalomyelitis in mice. J Exp Med 213(6):929-49 |
| abstractText | Growing evidence supports a role for IL-1 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), but how it impacts neuroinflammation is poorly understood. We show that susceptibility to EAE requires activation of IL-1R1 on radiation-resistant cells via IL-1beta secreted by bone marrow-derived cells. Neutrophils and monocyte-derived macrophages (MDMs) are the main source of IL-1beta and produce this cytokine as a result of their transmigration across the inflamed blood-spinal cord barrier. IL-1R1 expression in the spinal cord is found in endothelial cells (ECs) of the pial venous plexus. Accordingly, leukocyte infiltration at EAE onset is restricted to IL-1R1(+) subpial and subarachnoid vessels. In response to IL-1beta, primary cultures of central nervous system ECs produce GM-CSF, G-CSF, IL-6, Cxcl1, and Cxcl2. Initiation of EAE or subdural injection of IL-1beta induces a similar cytokine/chemokine signature in spinal cord vessels. Furthermore, the transfer of Gr1(+) cells on the spinal cord is sufficient to induce illness in EAE-resistant IL-1beta knockout (KO) mice. Notably, transfer of Gr1(+) cells isolated from C57BL/6 mice induce massive recruitment of recipient myeloid cells compared with cells from IL-1beta KO donors, and this recruitment translates into more severe paralysis. These findings suggest that an IL-1beta-dependent paracrine loop between infiltrated neutrophils/MDMs and ECs drives neuroinflammation. |
