Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1784835241902342144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9684245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT schadlichinessophie interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes AT vienhuesjonasheinrich interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes AT janderalina interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes AT piepkemarius interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes AT magnustim interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes AT lambertsenkatelykke interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes AT clausenbettinahjelm interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes AT gelderblommathias interleukin1mediatesischemicbraininjuryviainductionofil17aingdtcellsandcxcl1inastrocytes |