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Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition.
Cell ( IF 64.5 ) Pub Date : 2020-07-22 , DOI: 10.1016/j.cell.2020.06.026
Emanuela Pasciuto 1 , Oliver T Burton 2 , Carlos P Roca 2 , Vasiliki Lagou 1 , Wenson D Rajan 1 , Tom Theys 3 , Renzo Mancuso 4 , Raul Y Tito 5 , Lubna Kouser 2 , Zsuzsanna Callaerts-Vegh 6 , Alerie G de la Fuente 7 , Teresa Prezzemolo 1 , Loriana G Mascali 1 , Aleksandra Brajic 1 , Carly E Whyte 2 , Lidia Yshii 1 , Anna Martinez-Muriana 4 , Michelle Naughton 7 , Andrew Young 7 , Alena Moudra 2 , Pierre Lemaitre 1 , Suresh Poovathingal 8 , Jeroen Raes 5 , Bart De Strooper 9 , Denise C Fitzgerald 7 , James Dooley 2 , Adrian Liston 10
Affiliation  

The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems.

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中文翻译:

小胶质细胞需要 CD4 T 细胞来完成胎儿到成人的转变。

大脑是相对免疫特权的部位。尽管已经报道了 CD4 T 细胞存在于中枢神经系统中,但它们在健康大脑中的存在仍然存在争议,并且它们的功能在很大程度上仍然未知。我们结合使用成像、单细胞和手术方法来识别小鼠和人脑中的 CD69 + CD4 T 细胞群,与循环 CD4 T 细胞不同。大脑常驻人口是通过原位得出的与活化的循环细胞分化并由自身抗原和外周微生物组形成。单细胞测序显示,在没有鼠 CD4 T 细胞的情况下,驻留的小胶质细胞在胎儿和成人状态之间保持悬浮状态。这种成熟缺陷导致过多的未成熟神经元突触和行为异常。这些结果阐明了 CD4 T 细胞在大脑发育中的作用以及免疫系统和神经系统进化之间潜在的相互关联的动态。

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更新日期:2020-08-06
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