Abstract
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-1ß secreted by bone marrow-derived cells. Neutrophils and monocyte-derived macrophages (MDMs) are the main source of IL-1ß 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-1ß, 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-1ß 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-1ß 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-1ß KO donors, and this recruitment translates into more severe paralysis. These findings suggest that an IL-1ß-dependent paracrine loop between infiltrated neutrophils/MDMs and ECs drives neuroinflammation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 929-949 |
| Number of pages | 21 |
| Journal | Journal of Experimental Medicine |
| Volume | 213 |
| Issue number | 6 |
| DOIs | |
| State | Published - May 1 2016 |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Myeloid cell transmigration across the CNS vasculature triggers IL-1ß-driven neuroinflammation during autoimmune encephalomyelitis in mice. / Lévesque, Sébastien A.; Paré, Alexandre; Mailhot, Benoit; Bellver-Landete, Victor; Kébir, Hania; Lécuyer, Marc André; Alvarez, Jorge Ivan; Prat, Alexandre; de Rivero Vaccari, Juan Pablo P; Keane, Robert; Lacroix, Steve.
In: Journal of Experimental Medicine, Vol. 213, No. 6, 01.05.2016, p. 929-949.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Myeloid cell transmigration across the CNS vasculature triggers IL-1ß-driven neuroinflammation during autoimmune encephalomyelitis in mice
AU - Lévesque, Sébastien A.
AU - Paré, Alexandre
AU - Mailhot, Benoit
AU - Bellver-Landete, Victor
AU - Kébir, Hania
AU - Lécuyer, Marc André
AU - Alvarez, Jorge Ivan
AU - Prat, Alexandre
AU - de Rivero Vaccari, Juan Pablo P
AU - Keane, Robert
AU - Lacroix, Steve
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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-1ß secreted by bone marrow-derived cells. Neutrophils and monocyte-derived macrophages (MDMs) are the main source of IL-1ß 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-1ß, 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-1ß 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-1ß 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-1ß KO donors, and this recruitment translates into more severe paralysis. These findings suggest that an IL-1ß-dependent paracrine loop between infiltrated neutrophils/MDMs and ECs drives neuroinflammation.
AB - 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-1ß secreted by bone marrow-derived cells. Neutrophils and monocyte-derived macrophages (MDMs) are the main source of IL-1ß 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-1ß, 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-1ß 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-1ß 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-1ß KO donors, and this recruitment translates into more severe paralysis. These findings suggest that an IL-1ß-dependent paracrine loop between infiltrated neutrophils/MDMs and ECs drives neuroinflammation.
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U2 - 10.1084/jem.20151437
DO - 10.1084/jem.20151437
M3 - Article
C2 - 27139491
AN - SCOPUS:84971554433
VL - 213
SP - 929
EP - 949
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -