| First Author | Sanmarco LM | Year | 2021 |
| Journal | Nature | Volume | 590 |
| Issue | 7846 | Pages | 473-479 |
| PubMed ID | 33408417 | Mgi Jnum | J:325211 |
| Mgi Id | MGI:6710149 | Doi | 10.1038/s41586-020-03116-4 |
| Citation | Sanmarco LM, et al. (2021) Gut-licensed IFNgamma(+) NK cells drive LAMP1(+)TRAIL(+) anti-inflammatory astrocytes. Nature 590(7846):473-479 |
| abstractText | Astrocytes are glial cells that are abundant in the central nervous system (CNS) and that have important homeostatic and disease-promoting functions(1). However, little is known about the homeostatic anti-inflammatory activities of astrocytes and their regulation. Here, using high-throughput flow cytometry screening, single-cell RNA sequencing and CRISPR-Cas9-based cell-specific in vivo genetic perturbations in mice, we identify a subset of astrocytes that expresses the lysosomal protein LAMP1(2) and the death receptor ligand TRAIL(3). LAMP1(+)TRAIL(+) astrocytes limit inflammation in the CNS by inducing T cell apoptosis through TRAIL-DR5 signalling. In homeostatic conditions, the expression of TRAIL in astrocytes is driven by interferon-gamma (IFNgamma) produced by meningeal natural killer (NK) cells, in which IFNgamma expression is modulated by the gut microbiome. TRAIL expression in astrocytes is repressed by molecules produced by T cells and microglia in the context of inflammation. Altogether, we show that LAMP1(+)TRAIL(+) astrocytes limit CNS inflammation by inducing T cell apoptosis, and that this astrocyte subset is maintained by meningeal IFNgamma(+) NK cells that are licensed by the microbiome. |
