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

Authors

  • Y. Pan
  • M. Xiong
  • R. Chen
  • Y. Ma
  • C. Corman
  • M. Maricos
  • U. Kindler
  • M. Semtner
  • Y.H. Chen
  • S. Dahiya
  • D.H. Gutmann

Journal

  • Genes & Development

Citation

  • Genes Dev 32 (7-8): 491-496

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.


DOI

doi:10.1101/gad.310797.117