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无胸腺小鼠揭示了 T 细胞-小胶质细胞相互作用在建立支持低级别神经胶质瘤生长的微环境中的必要性。

Athymic mice reveal a requirement for T-cell-microglia interactions in establishing a microenvironment supportive of low-grade glioma growth.

机构信息

Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Genes Dev. 2018 Apr 1;32(7-8):491-496. doi: 10.1101/gad.310797.117. Epub 2018 Apr 9.

Abstract

Pediatric low-grade gliomas (LGGs) frequently do not engraft in immunocompromised mice, limiting their use as an experimental platform. In contrast, murine Neurofibromatosis-1 () optic LGG stem cells (o-GSCs) form glioma-like lesions in wild-type, but not athymic, mice following transplantation. Here, we show that the inability of athymic mice to support o-GSC engraftment results from impaired microglia/macrophage function, including reduced expression of Ccr2 and Ccl5, both of which are required for o-GSC engraftment and optic glioma growth. Impaired Ccr2 and Ccl5 expression in athymic microglia/macrophages was restored by T-cell exposure, establishing T-cell-microglia/macrophage interactions as critical stromal determinants that support NF1 LGG growth.

摘要

小儿低度神经胶质瘤(LGGs)通常不能在免疫功能低下的小鼠中植入,限制了它们作为实验平台的应用。相比之下,鼠类神经纤维瘤病 1()视神经 LGG 干细胞(o-GSCs)在移植后会在野生型小鼠中形成类胶质瘤病变,但不会在无胸腺小鼠中形成。在这里,我们表明,无胸腺小鼠无法支持 o-GSC 植入是由于小胶质细胞/巨噬细胞功能受损所致,包括 Ccr2 和 Ccl5 的表达减少,这两者都是 o-GSC 植入和视神经胶质瘤生长所必需的。T 细胞暴露恢复了无胸腺小胶质细胞/巨噬细胞中 Ccr2 和 Ccl5 的表达,证明了 T 细胞-小胶质细胞/巨噬细胞相互作用是支持 NF1 LGG 生长的关键基质决定因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daf0/5959233/019ad504f1c0/491f01.jpg

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