Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice
Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice
复制标题
抑制 Dectin-1 通过调节小鼠脑出血后小胶质细胞/巨噬细胞表型改善神经炎症
DOI：
10.1007/s12975-021-00889-2
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发表时间：
2021-02-04
影响因子：
6.9
通讯作者：
Chen, Gao
中科院分区：
文献类型：
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作者：
Fu, Xiongjie;Zeng, Hanhai;Chen, Gao
小胶质细胞/巨噬细胞向炎症表型的极化是脑出血(ICH)后神经炎症的重要因素。Dectin-1是一种模式识别受体，已被报道在调节缺血性中风和脊髓损伤的神经炎症中发挥关键作用。然而，Dectin-1在脑出血后的作用和作用机制尚不清楚。本研究探讨Dectin-1对脑出血后小胶质细胞/巨噬细胞表型和神经炎症的调节作用及其可能的机制。我们发现脑出血后Dectin-1的表达增加，并且主要定位于小胶质细胞/巨噬细胞。脑出血后中性粒细胞浸润增加，小胶质细胞/巨噬细胞偏向炎症表型。然而，Dectin-1抑制剂的治疗逆转了这些现象，并诱导了小胶质细胞/巨噬细胞抗炎表型的转变；这导致了神经功能障碍的缓解，并促进了脑出血后血肿的清除。我们还发现，Dectin-1在体内和体外都通过激活脾酪氨酸激酶(Syk)与下游的促炎途径CARD9/NF-κB发生串扰。总之，我们的数据表明Dectin-1参与了脑出血后小胶质细胞/巨噬细胞的极化和功能恢复，并且这一机制至少部分地参与了Syk/CARD9/NF-kB通路的参与。
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.