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Myeloid cell transmigration across the CNS vasculature triggers IL-1β–driven neuroinflammation during autoimmune encephalomyelitis in mice
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-1β secreted by bone mar...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886360/ https://www.ncbi.nlm.nih.gov/pubmed/27139491 http://dx.doi.org/10.1084/jem.20151437 |
Sumario: | 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-1β secreted by bone marrow–derived cells. Neutrophils and monocyte-derived macrophages (MDMs) are the main source of IL-1β 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-1β, 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-1β 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-1β 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-1β KO donors, and this recruitment translates into more severe paralysis. These findings suggest that an IL-1β–dependent paracrine loop between infiltrated neutrophils/MDMs and ECs drives neuroinflammation. |
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