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Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke

BACKGROUND: Subtle adjustment of the activation status of CNS resident microglia and peripheral macrophages, to promote their neuroprotective and neuroregenerative functions, may facilitate research towards curing neurodegenerative disorders. In the present study, we investigated whether targeted in...

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Autores principales: Hamzei Taj, Somayyeh, Le Blon, Debbie, Hoornaert, Chloé, Daans, Jasmijn, Quarta, Alessandra, Praet, Jelle, Van der Linden, Annemie, Ponsaerts, Peter, Hoehn, Mathias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987479/
https://www.ncbi.nlm.nih.gov/pubmed/29866203
http://dx.doi.org/10.1186/s12974-018-1212-7
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author Hamzei Taj, Somayyeh
Le Blon, Debbie
Hoornaert, Chloé
Daans, Jasmijn
Quarta, Alessandra
Praet, Jelle
Van der Linden, Annemie
Ponsaerts, Peter
Hoehn, Mathias
author_facet Hamzei Taj, Somayyeh
Le Blon, Debbie
Hoornaert, Chloé
Daans, Jasmijn
Quarta, Alessandra
Praet, Jelle
Van der Linden, Annemie
Ponsaerts, Peter
Hoehn, Mathias
author_sort Hamzei Taj, Somayyeh
collection PubMed
description BACKGROUND: Subtle adjustment of the activation status of CNS resident microglia and peripheral macrophages, to promote their neuroprotective and neuroregenerative functions, may facilitate research towards curing neurodegenerative disorders. In the present study, we investigated whether targeted intracerebral delivery of the anti-inflammatory cytokine interleukin (IL)13, by means of transplanting IL13-expressing mesenchymal stem cells (IL13-MSCs), can promote a phenotypic switch in both microglia and macrophages during the pro-inflammatory phase in a mouse model of ischemic stroke. METHODS: We used the CX(3)CR1(eGFP/+) CCR2(RFP/+) transgenic mouse model to separately recognize brain-resident microglia from infiltrated macrophages. Quantitative immunohistochemical analyses were applied to characterize polarization phenotypes of both cell types. RESULTS: Distinct behaviors of both cell populations were noted dependent on the anatomical site of the lesion. Immunohistochemistry revealed that mice grafted with IL13-MSCs, in contrast to non-grafted and MSC-grafted control mice, were able to drive recruited microglia and macrophages into an alternative activation state, as visualized by a significant increase of Arg-1 and a noticeable decrease of MHC-II expression at day 14 after ischemic stroke. Interestingly, both Arg-1 and MHC-II were expressed more abundantly in macrophages than in microglia, further confirming the distinct behavior of both cell populations. CONCLUSIONS: The current data highlight the importance of controlled and localized delivery of the anti-inflammatory cytokine IL13 for modulation of both microglia and macrophage responses after ischemic stroke, thereby providing pre-clinical rationale for the application of L13-MSCs in future investigations of neurodegenerative disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-018-1212-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-59874792018-07-10 Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke Hamzei Taj, Somayyeh Le Blon, Debbie Hoornaert, Chloé Daans, Jasmijn Quarta, Alessandra Praet, Jelle Van der Linden, Annemie Ponsaerts, Peter Hoehn, Mathias J Neuroinflammation Research BACKGROUND: Subtle adjustment of the activation status of CNS resident microglia and peripheral macrophages, to promote their neuroprotective and neuroregenerative functions, may facilitate research towards curing neurodegenerative disorders. In the present study, we investigated whether targeted intracerebral delivery of the anti-inflammatory cytokine interleukin (IL)13, by means of transplanting IL13-expressing mesenchymal stem cells (IL13-MSCs), can promote a phenotypic switch in both microglia and macrophages during the pro-inflammatory phase in a mouse model of ischemic stroke. METHODS: We used the CX(3)CR1(eGFP/+) CCR2(RFP/+) transgenic mouse model to separately recognize brain-resident microglia from infiltrated macrophages. Quantitative immunohistochemical analyses were applied to characterize polarization phenotypes of both cell types. RESULTS: Distinct behaviors of both cell populations were noted dependent on the anatomical site of the lesion. Immunohistochemistry revealed that mice grafted with IL13-MSCs, in contrast to non-grafted and MSC-grafted control mice, were able to drive recruited microglia and macrophages into an alternative activation state, as visualized by a significant increase of Arg-1 and a noticeable decrease of MHC-II expression at day 14 after ischemic stroke. Interestingly, both Arg-1 and MHC-II were expressed more abundantly in macrophages than in microglia, further confirming the distinct behavior of both cell populations. CONCLUSIONS: The current data highlight the importance of controlled and localized delivery of the anti-inflammatory cytokine IL13 for modulation of both microglia and macrophage responses after ischemic stroke, thereby providing pre-clinical rationale for the application of L13-MSCs in future investigations of neurodegenerative disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-018-1212-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-04 /pmc/articles/PMC5987479/ /pubmed/29866203 http://dx.doi.org/10.1186/s12974-018-1212-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hamzei Taj, Somayyeh
Le Blon, Debbie
Hoornaert, Chloé
Daans, Jasmijn
Quarta, Alessandra
Praet, Jelle
Van der Linden, Annemie
Ponsaerts, Peter
Hoehn, Mathias
Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke
title Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke
title_full Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke
title_fullStr Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke
title_full_unstemmed Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke
title_short Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke
title_sort targeted intracerebral delivery of the anti-inflammatory cytokine il13 promotes alternative activation of both microglia and macrophages after stroke
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987479/
https://www.ncbi.nlm.nih.gov/pubmed/29866203
http://dx.doi.org/10.1186/s12974-018-1212-7
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