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Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice

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Abstract

Polarization of microglia/macrophages toward the pro-inflammatory phenotype is an important contributor to neuroinflammation after intracerebral hemorrhage (ICH). Dectin-1 is a pattern recognition receptor that has been reported to play a key role in regulating neuroinflammation in ischemic stroke and spinal cord injury. However, the role and mechanism of action of Dectin-1 after ICH remains unclear. In this study, we investigated the effect of Dectin-1 on modulating the microglia/macrophage phenotype and neuroinflammation and the possible underlying mechanism after ICH. We found that Dectin-1 expression increased after ICH, and was mainly localized in microglia/macrophages. Neutrophil infiltration and microglia/macrophage polarization toward the pro-inflammatory phenotype increased after ICH. However, treatment with a Dectin-1 inhibitor reversed these phenomena and induced a shift the anti-inflammatory phenotype in microglia/macrophages; this resulted in alleviation of neurological dysfunction and facilitated hematoma clearance after ICH. We also found that Dectin-1 crosstalks with the downstream pro-inflammatory pathway, Card9/NF-κB, by activating spleen tyrosine kinase (Syk) both in vivo and in vitro. In conclusion, our data suggest that Dectin-1 is involved in the microglia/macrophage polarization and functional recovery after ICH, and that this mechanism, at least in part, may contribute to the involvement of the Syk/Card9/NF-kB pathway.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Key R &D program of China (No. 2018YFC1312600 and No. 2018YFC1312603), National Nature Science Foundation of China (No. 81870910), the Key Research and Development Project of Zhejiang Province (No.2018C03011), and Project of Zhejiang Provincial Nature Science Foundation (No. LY18H090007).

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  1. Xiongjie Fu, Hanhai Zeng and Jikuang Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Jiefang Road 88th, Hangzhou, 310016, China

    Xiongjie Fu, Hanhai Zeng, Jikuang Zhao, Guoyang Zhou, Hang Zhou, Jianfeng Zhuang, Chaoran Xu, Jianru Li, Yucong Peng, Yang Cao, Yin Li, Huaijun Chen, Lin Wang, Feng Yan & Gao Chen

  2. Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital, Zhejiang University School of Medicine, Ningbo, China

    Jikuang Zhao

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  1. Xiongjie Fu
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Contributions

GC, FY, and LW conceived and designed the study. XJF, HHZ, JKZ, and GYZ performed the ICH model and PCR. HZ, JFZ, and CRX performed the western blots and immunostaining. YCP, YC, and HJC prepared the figures. YL and JRL analyzed data. HZ, GYZ, and XJF performed cell culture. XJF, HHZ, JKZ, and GYZ prepared the manuscript draft. GC, YF, and LW wrote the paper.

Corresponding authors

Correspondence to Feng Yan or Gao Chen.

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All procedures were performed according to the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and were approved by the Institutional Ethics Committee of the Second Affiliated Hospital, Zhejiang University of Medicine.

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The original online version of this article was revised: there was an error in Figure 1b.

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Fu, X., Zeng, H., Zhao, J. et al. Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice. Transl. Stroke Res. 12, 1018–1034 (2021). https://doi.org/10.1007/s12975-021-00889-2

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