Department of Cell Biology, Physiology and Immunology, Universitat Autonoma Barcelona, Barcelona, Spain ; Institute of Neuroscience, Universitat Autonoma Barcelona, Barcelona, Spain.
PLoS One. 2013 Aug 19;8(8):e72083. doi: 10.1371/journal.pone.0072083. eCollection 2013.
During postnatal development, microglia, the resident innate immune cells of the central nervous system are constantly monitoring the brain parenchyma, cleaning the cell debris, the synaptic contacts overproduced and also maintaining the brain homeostasis. In this context, the postnatal microglia need some control over the innate immune response. One such molecule recently described to be involved in modulation of immune response is TREM2 (triggering receptor expressed on myeloid cells 2). Although some studies have observed TREM2 mRNA in postnatal brain, the regional pattern of the TREM2 protein has not been described. We therefore characterized the distribution of TREM2 protein in mice brain from Postnatal day (P) 1 to 14 by immunostaining. In our study, TREM2 protein was expressed only in microglia/macrophages and is developmentally downregulated in a region-dependent manner. Its expression persisted in white matter, mainly in caudal corpus callosum, and the neurogenic subventricular zone for a longer time than in grey matter. Additionally, the phenotypes of the TREM2+ microglia also differ; expressing CD16/32, MHCII and CD86 (antigen presentation markers) and CD68 (phagocytic marker) in different regions as well as with different intensity till P7. The mannose receptor (CD206) colocalized with TREM2 only at P1-P3 in the subventricular zone and cingulum, while others persisted at low intensities till P7. Furthermore, the spatiotemporal expression pattern and characterization of TREM2 indicate towards its other plausible roles in phagocytosis, progenitor's fate determination or microglia phenotype modulation during postnatal development. Hence, the increase of TREM2 observed in pathologies may recapitulate their function during postnatal development, as a better understanding of this period may open new pathway for future therapies.
在出生后发育过程中，小胶质细胞作为中枢神经系统的固有免疫细胞，不断监测脑实质，清除细胞碎片、突触接触过度产生的物质，同时维持脑内环境稳态。在此背景下，出生后小胶质细胞需要对固有免疫反应进行一定的控制。最近发现一种参与免疫反应调节的分子是 TREM2（髓样细胞触发受体 2）。虽然一些研究已经观察到出生后大脑中的 TREM2 mRNA，但 TREM2 蛋白的区域模式尚未描述。因此，我们通过免疫染色来描述 TREM2 蛋白在出生后 1 至 14 天的小鼠大脑中的分布。在我们的研究中，TREM2 蛋白仅在小胶质细胞/巨噬细胞中表达，并以区域依赖性方式发育下调。它的表达在白质中持续存在，主要在尾部胼胝体和神经发生的侧脑室下区，比灰质中持续的时间更长。此外，TREM2+小胶质细胞的表型也不同；在不同区域表达 CD16/32、MHCII 和 CD86（抗原呈递标记物）和 CD68（吞噬标记物），其表达强度在 P7 前不同。甘露糖受体（CD206）仅在侧脑室下区和扣带区与 TREM2 在 P1-P3 时共表达，而其他标志物则持续表达至 P7，表达强度较低。此外，TREM2 的时空表达模式和特征表明其在吞噬作用、祖细胞命运决定或出生后发育中小胶质细胞表型调节中具有其他可能的作用。因此，在病理状态下观察到的 TREM2 增加可能反映了其在出生后发育过程中的作用，因为更好地了解这一时期可能为未来的治疗开辟新途径。
