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J Neuroinflammation. 2018 Jun 4;15(1):174. doi: 10.1186/s12974-018-1212-7.

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

Author information

1
In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.
2
Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium.
3
Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.
4
Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
5
In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany. mathias@sf.mpg.de.
6
Department of Radiology, Leiden University Medical Center, Leiden, Netherlands. mathias@sf.mpg.de.

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.

KEYWORDS:

Interleukin 13; Mesenchymal stem cells; Microglia/macrophage polarization; Neuroinflammation; Stroke

PMID:
29866203
PMCID:
PMC5987479
DOI:
10.1186/s12974-018-1212-7
[Indexed for MEDLINE]
Free PMC Article

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