期刊
JOURNAL OF NEUROINFLAMMATION
卷 15, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12974-018-1212-7
关键词
Stroke; Microglia/macrophage polarization; Interleukin 13; Mesenchymal stem cells; Neuroinflammation
资金
- EU [HEALTH-F2-2012-279017, PIAPP-GA-2013-612360]
- University of Antwerp (Belgium)
- Fund for Scientific Research (FWO)-Flanders [G091518N]
- Belgian Charcot Foundation
- FWO
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据