| Autor: |
Henrik Heiland, Dieter, Ravi, Vidhya M., Behringer, Simon P., Frenking, Jan Hendrik, Wurm, Julian, Joseph, Kevin, Garrelfs, Nicklas W. C., Strähle, Jakob, Heynckes, Sabrina, Grauvogel, Jürgen, Franco, Pamela, Mader, Irina, Schneider, Matthias, Potthoff, Anna-Laura, Delev, Daniel, Hofmann, Ulrich G., Fung, Christian, Beck, Jürgen, Sankowski, Roman, Prinz, Marco |
| Zdroj: |
Nature Communications; 6/11/2019, Vol. 10 Issue 1, pN.PAG-N.PAG, 1p |
| Abstrakt: |
Reactive astrocytes evolve after brain injury, inflammatory and degenerative diseases, whereby they undergo transcriptomic re-programming. In malignant brain tumors, their function and crosstalk to other components of the environment is poorly understood. Here we report a distinct transcriptional phenotype of reactive astrocytes from glioblastoma linked to JAK/STAT pathway activation. Subsequently, we investigate the origin of astrocytic transformation by a microglia loss-of-function model in a human organotypic slice model with injected tumor cells. RNA-seq based gene expression analysis of astrocytes reveals a distinct astrocytic phenotype caused by the coexistence of microglia and astrocytes in the tumor environment, which leads to a large release of anti-inflammatory cytokines such as TGFβ, IL10 and G-CSF. Inhibition of the JAK/STAT pathway shifts the balance of pro- and anti-inflammatory cytokines towards a pro-inflammatory environment. The complex interaction of astrocytes and microglia cells promotes an immunosuppressive environment, suggesting that tumor-associated astrocytes contribute to anti-inflammatory responses. Astrocytes play important roles in neuroinflammatory diseases. Here the authors characterize human glioblastoma-associated astrocytes by gene expression and demonstrate their immunosuppressive role promoted by interactions with tumor and microglia cells in an organotypic model. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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