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Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes

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 (α/β) knockout (Il1(−/−)) and wildtype (WT) littermate m...

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Autores principales: Schädlich, Ines Sophie, Vienhues, Jonas Heinrich, Jander, Alina, Piepke, Marius, Magnus, Tim, Lambertsen, Kate Lykke, Clausen, Bettina Hjelm, Gelderblom, Mathias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684245/
https://www.ncbi.nlm.nih.gov/pubmed/35384588
http://dx.doi.org/10.1007/s12017-022-08709-y
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author Schädlich, Ines Sophie
Vienhues, Jonas Heinrich
Jander, Alina
Piepke, Marius
Magnus, Tim
Lambertsen, Kate Lykke
Clausen, Bettina Hjelm
Gelderblom, Mathias
author_facet Schädlich, Ines Sophie
Vienhues, Jonas Heinrich
Jander, Alina
Piepke, Marius
Magnus, Tim
Lambertsen, Kate Lykke
Clausen, Bettina Hjelm
Gelderblom, Mathias
author_sort Schädlich, Ines Sophie
collection PubMed
description 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 (α/β) 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 γδ T cells and astrocytes as target cells of IL-1 signaling-mediated neutrophil recruitment. First, IL-1-induced IL-17A production in γδ 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12017-022-08709-y.
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spelling pubmed-96842452022-11-25 Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes Schädlich, Ines Sophie Vienhues, Jonas Heinrich Jander, Alina Piepke, Marius Magnus, Tim Lambertsen, Kate Lykke Clausen, Bettina Hjelm Gelderblom, Mathias Neuromolecular Med Original Paper 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 (α/β) 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 γδ T cells and astrocytes as target cells of IL-1 signaling-mediated neutrophil recruitment. First, IL-1-induced IL-17A production in γδ 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12017-022-08709-y. Springer US 2022-04-06 2022 /pmc/articles/PMC9684245/ /pubmed/35384588 http://dx.doi.org/10.1007/s12017-022-08709-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
Schädlich, Ines Sophie
Vienhues, Jonas Heinrich
Jander, Alina
Piepke, Marius
Magnus, Tim
Lambertsen, Kate Lykke
Clausen, Bettina Hjelm
Gelderblom, Mathias
Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
title Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
title_full Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
title_fullStr Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
title_full_unstemmed Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
title_short Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
title_sort interleukin-1 mediates ischemic brain injury via induction of il-17a in γδ t cells and cxcl1 in astrocytes
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684245/
https://www.ncbi.nlm.nih.gov/pubmed/35384588
http://dx.doi.org/10.1007/s12017-022-08709-y
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