Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation.

Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation.
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假定的小胶质细胞特异性标记的潜在警告,以评估与年龄相关的脑血管神经炎症。

DOI:
10.1186/s12974-020-02019-5
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发表时间:
2020-12-01
影响因子:
9.3
通讯作者:
McCullough LD
McCullough LD
中科院分区:
医学1区
文献类型:
--
作者:
Honarpisheh P;Lee J;Banerjee A;Blasco-Conesa MP;Honarpisheh P;d'Aigle J;Mamun AA;Ritzel RM;Chauhan A;Ganesh BP;McCullough LD

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通过基于流式细胞术的表面表型分析区分常驻小胶质细胞和浸润性髓样细胞的能力是检查年龄相关神经炎症的重要技术。用于鉴定小胶质细胞的最常用的表面标志物包括CD 45(低-中等表达)、CD 11b、Tmem 119和P2 RY 12。在这项研究中,我们研究了这些推定的小胶质细胞标志物在体内中风,脑淀粉样血管病(CAA),衰老以及在离体LPS诱导的炎症模型的动物模型的表达水平的变化。我们证明,Tmem 119和P2 RY 12的表达是明显的,在两个CD 45 int和CD 45 high髓细胞群体中的中风,CAA和老化的模型。有趣的是,LPS刺激FACS分选的成人小胶质细胞表明,这些脑驻留骨髓细胞可以上调CD 45,下调Tmem 119和P2 RY 12,使它们与外周来源的骨髓细胞群无法区分。重要的是,我们的研究结果表明,小胶质细胞分子特征的这些变化可以在没有其他脑驻留或外周来源的免疫细胞的贡献的情况下发生。我们建议未来的研究谨慎地通过流式细胞术识别小胶质细胞,特别是在没有使用针对特定神经炎症模型验证的标记物组合的情况下。居住在“浸润性髓样”人群中的常驻小胶质细胞亚群,尽管很小,但在维持大脑中的免疫警戒方面可能具有重要的功能,因此在神经免疫学研究中不应忽视。在线版本包含补充材料,可在10.1186/s12974-020-02019-5获得。
The ability to distinguish resident microglia from infiltrating myeloid cells by flow cytometry-based surface phenotyping is an important technique for examining age-related neuroinflammation. The most commonly used surface markers for the identification of microglia include CD45 (low-intermediate expression), CD11b, Tmem119, and P2RY12. In this study, we examined changes in expression levels of these putative microglia markers in in vivo animal models of stroke, cerebral amyloid angiopathy (CAA), and aging as well as in an ex vivo LPS-induced inflammation model. We demonstrate that Tmem119 and P2RY12 expression is evident within both CD45int and CD45high myeloid populations in models of stroke, CAA, and aging. Interestingly, LPS stimulation of FACS-sorted adult microglia suggested that these brain-resident myeloid cells can upregulate CD45 and downregulate Tmem119 and P2RY12, making them indistinguishable from peripherally derived myeloid populations. Importantly, our findings show that these changes in the molecular signatures of microglia can occur without a contribution from the other brain-resident or peripherally sourced immune cells. We recommend future studies approach microglia identification by flow cytometry with caution, particularly in the absence of the use of a combination of markers validated for the specific neuroinflammation model of interest. The subpopulation of resident microglia residing within the “infiltrating myeloid” population, albeit small, may be functionally important in maintaining immune vigilance in the brain thus should not be overlooked in neuroimmunological studies. The online version contains supplementary material available at 10.1186/s12974-020-02019-5.
LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
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