Athymic mice reveal a requirement for T-cell–microglia interactions in establishing a microenvironment supportive of Nf1 low-grade glioma growth

Yuan Pan; Min Xiong; Ran Chen; Yu Ma; Courtney Corman; Meron Maricos; Urs Kindler; Marcus Semtner; Yi-Hsien Chen; Sonika Dahiya; David H. Gutmann

doi:10.1101/gad.310797.117

Athymic mice reveal a requirement for T-cell–microglia interactions in establishing a microenvironment supportive of Nf1 low-grade glioma growth

¹Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA;
²Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
³Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany;
⁴Genome Engineering and iPSC Center (GEIC), Washington University School of Medicine, St. Louis, Missouri 63110, USA;
⁵Division of Neuropathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA

Corresponding author: gutmannd{at}wustl.edu

↵6 These authors contributed equally to this work.

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 (Nf1) 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 Nf1 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.

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Footnotes

Supplemental material is available for this article.
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.310797.117.

Received December 12, 2017.
Accepted March 13, 2018.

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