期刊
NEUROMOLECULAR MEDICINE
卷 24, 期 4, 页码 437-451出版社
HUMANA PRESS INC
DOI: 10.1007/s12017-022-08709-y
关键词
Ischemic stroke; Inflammation; Interleukin-1; gamma delta T cells; Interleukin-17A; Astrocytes; CXCL1
资金
- Projekt DEAL
- DFG Research Unit FOR 2879 From immune cells to stroke recovery [428778375]
- Landesforschungsforderung Hamburg [LFF-OS 77-2019]
- Brodrene Hartmann Fonden
- Toyota Foundation
IL-1 exacerbates post-stroke inflammation and its neutralization is protective. This study identifies gamma delta T cells and astrocytes as target cells of IL-1 signaling-mediated neutrophil recruitment. The study also highlights the important roles of IL-17A and CXCL1 in this process.
As a prototypical proinflammatory cytokine, interleukin-1 (IL-1) exacerbates the early post-stroke inflammation, whereas its neutralization is protective. To further investigate the underlying cell-type-specific IL-1 effects, we subjected IL-1 (alpha/beta) knockout (Il1(-/-)) and wildtype (WT) littermate mice to permanent middle cerebral artery occlusion (pMCAO) and assessed immune cell infiltration and cytokine production in the ischemic hemisphere by flow cytometry 24 h and 72 h after stroke. Il1(-/-) mice showed smaller infarcts and reduced neutrophil infiltration into the ischemic brain. We identified gamma delta T cells and astrocytes as target cells of IL-1 signaling-mediated neutrophil recruitment. First, IL-1-induced IL-17A production in gamma delta T cells in vivo, and IL-17A enhanced the expression of the main neutrophil attracting chemokine CXCL1 by astrocytes in the presence of tumor necrosis factor (TNF) in vitro. Second, IL-1 itself was a potent activator of astrocytic CXCL1 production in vitro. By employing a novel FACS sorting strategy for the acute isolation of astrocytes from ischemic brains, we confirmed that IL-1 is pivotal for Cxcl1 upregulation in astrocytes in vivo. Our results underscore the pleiotropic effects of IL-1 on immune and non-immune cells within the CNS to mount and amplify the post-stroke inflammatory response.
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