Differential modulation of TREM2 protein during postnatal brain development in mice.
Differential modulation of TREM2 protein during postnatal brain development in mice.
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DOI：
10.1371/journal.pone.0072083
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Giménez-Llort L
中科院分区：
文献类型：
--
作者：
Chertoff M;Shrivastava K;Gonzalez B;Acarin L;Giménez-Llort L
在出生后的发育过程中，小胶质细胞——中枢神经系统中的固有免疫细胞，不断监测脑实质，清理细胞碎片、过度产生的突触连接，并维持脑内稳态。在此背景下，出生后的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（髓样细胞表达的触发受体2）。尽管一些研究已经在出生后的大脑中观察到TREM2 mRNA，但TREM2蛋白的区域分布模式尚未被描述。因此，我们通过免疫染色对出生后第1天（P1）到第14天小鼠大脑中TREM2蛋白的分布进行了表征。在我们的研究中，TREM2蛋白仅在小胶质细胞/巨噬细胞中表达，并且以区域依赖的方式在发育过程中下调。它在白质中的表达持续时间比在灰质中长，主要在胼胝体尾部和神经发生的室下区。此外，TREM2+小胶质细胞的表型也不同；在不同区域以及直到P7时以不同强度表达CD16/32、MHCII和CD86（抗原呈递标记物）以及CD68（吞噬标记物）。甘露糖受体（CD206）仅在P1 - P3时在室下区和扣带与TREM2共定位，而其他的则以低强度持续到P7。此外，TREM2的时空表达模式和特征表明它在出生后发育过程中在吞噬作用、祖细胞命运决定或小胶质细胞表型调节方面可能具有其他作用。因此，在病理状态下观察到的TREM2增加可能重现其在出生后发育过程中的功能，因为对这一时期的更好理解可能为未来的治疗开辟新的途径。
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.
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DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
3.3
作者：
BO, L;MORK, S;TRAPP, BD
通讯作者：
TRAPP, BD
影响因子：
2.5
作者：
Billiards, Saraid S.;Haynes, Robin L.;Kinney, Hannah C.
通讯作者：
Kinney, Hannah C.
影响因子：
25
作者：
Davalos, D;Grutzendler, J;Gan, WB
通讯作者：
Gan, WB
影响因子：
16.8
作者：
Derecki NC;Cronk JC;Kipnis J
通讯作者：
Kipnis J