Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke
Abstract 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 tar...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2018-06-01
|
Series: | Journal of Neuroinflammation |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12974-018-1212-7 |
id |
doaj-0dca64c90b82443bbd6db5779309b184 |
---|---|
record_format |
Article |
spelling |
doaj-0dca64c90b82443bbd6db5779309b1842020-11-25T02:09:26ZengBMCJournal of Neuroinflammation1742-20942018-06-0115111710.1186/s12974-018-1212-7Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after strokeSomayyeh Hamzei Taj0Debbie Le Blon1Chloé Hoornaert2Jasmijn Daans3Alessandra Quarta4Jelle Praet5Annemie Van der Linden6Peter Ponsaerts7Mathias Hoehn8In-vivo-NMR Laboratory, Max Planck Institute for Metabolism ResearchLaboratory of Experimental Hematology, University of AntwerpLaboratory of Experimental Hematology, University of AntwerpLaboratory of Experimental Hematology, University of AntwerpLaboratory of Experimental Hematology, University of AntwerpBio-Imaging Laboratory, University of AntwerpBio-Imaging Laboratory, University of AntwerpLaboratory of Experimental Hematology, University of AntwerpIn-vivo-NMR Laboratory, Max Planck Institute for Metabolism ResearchAbstract 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 CX3CR1eGFP/+ CCR2RFP/+ 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.http://link.springer.com/article/10.1186/s12974-018-1212-7StrokeMicroglia/macrophage polarizationInterleukin 13Mesenchymal stem cellsNeuroinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Somayyeh Hamzei Taj Debbie Le Blon Chloé Hoornaert Jasmijn Daans Alessandra Quarta Jelle Praet Annemie Van der Linden Peter Ponsaerts Mathias Hoehn |
spellingShingle |
Somayyeh Hamzei Taj Debbie Le Blon Chloé Hoornaert Jasmijn Daans Alessandra Quarta Jelle Praet Annemie Van der Linden Peter Ponsaerts Mathias Hoehn Targeted intracerebral delivery of the anti-inflammatory cytokine IL13 promotes alternative activation of both microglia and macrophages after stroke Journal of Neuroinflammation Stroke Microglia/macrophage polarization Interleukin 13 Mesenchymal stem cells Neuroinflammation |
author_facet |
Somayyeh Hamzei Taj Debbie Le Blon Chloé Hoornaert Jasmijn Daans Alessandra Quarta Jelle Praet Annemie Van der Linden Peter Ponsaerts Mathias Hoehn |
author_sort |
Somayyeh Hamzei Taj |
title |
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_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_sort |
targeted intracerebral delivery of the anti-inflammatory cytokine il13 promotes alternative activation of both microglia and macrophages after stroke |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2018-06-01 |
description |
Abstract 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 CX3CR1eGFP/+ CCR2RFP/+ 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. |
topic |
Stroke Microglia/macrophage polarization Interleukin 13 Mesenchymal stem cells Neuroinflammation |
url |
http://link.springer.com/article/10.1186/s12974-018-1212-7 |
work_keys_str_mv |
AT somayyehhamzeitaj targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT debbieleblon targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT chloehoornaert targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT jasmijndaans targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT alessandraquarta targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT jellepraet targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT annemievanderlinden targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT peterponsaerts targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke AT mathiashoehn targetedintracerebraldeliveryoftheantiinflammatorycytokineil13promotesalternativeactivationofbothmicrogliaandmacrophagesafterstroke |
_version_ |
1724923808608944128 |