Athymic mice reveal a requirement for T-cell-microglia interactions in establishing a microenvironment supportive of Nf1 low-grade glioma growth.
Yuan PanMin XiongRan ChenYu MaCourtney CormanMeron MaricosUrs KindlerMarcus SemtnerYi-Hsien ChenSonika DahiyaDavid H GutmannPublished in: Genes & development (2018)
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.
Keyphrases
- low grade
- wild type
- high grade
- signaling pathway
- lps induced
- stem cells
- inflammatory response
- high fat diet induced
- poor prognosis
- nuclear factor
- oxidative stress
- pi k akt
- neuropathic pain
- adipose tissue
- dendritic cells
- magnetic resonance imaging
- computed tomography
- high throughput
- magnetic resonance
- insulin resistance
- liver injury
- type diabetes
- skeletal muscle
- single cell
- immune response
- young adults