Reference - Detail
| RRC ID | 87000 |
|---|---|
| Author | Sanmarco LM, Wheeler MA, Gutiérrez-Vázquez C, Polonio CM, Linnerbauer M, Pinho-Ribeiro FA, Li Z, Giovannoni F, Batterman KV, Scalisi G, Zandee SEJ, Heck ES, Alsuwailm M, Rosene DL, Becher B, Chiu IM, Prat A, Quintana FJ. |
| Title | Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes. |
| Journal | Nature |
| Abstract |
Astrocytes are glial cells that are abundant in the central nervous system (CNS) and that have important homeostatic and disease-promoting functions1. 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 LAMP12 and the death receptor ligand TRAIL3. 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-γ (IFNγ) produced by meningeal natural killer (NK) cells, in which IFNγ 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 IFNγ+ NK cells that are licensed by the microbiome. |
| Volume | 590(7846) |
| Pages | 473-479 |
| Published | 2021-2-1 |
| DOI | 10.1038/s41586-020-03116-4 |
| PII | 10.1038/s41586-020-03116-4 |
| PMID | 33408417 |
| PMC | PMC8039910 |
| MeSH | Animals Apoptosis Astrocytes / immunology* Astrocytes / metabolism Biomarkers Central Nervous System / immunology Encephalomyelitis, Autoimmune, Experimental / immunology Encephalomyelitis, Autoimmune, Experimental / prevention & control Female Gastrointestinal Microbiome / immunology* Homeostasis Humans Inflammation / immunology Inflammation / prevention & control* Interferon-gamma / immunology* Killer Cells, Natural / immunology* Lysosomal Membrane Proteins / metabolism* Lysosomal-Associated Membrane Protein 1 Meninges / cytology Meninges / immunology Mice Mice, Inbred C57BL T-Lymphocytes / cytology T-Lymphocytes / immunology TNF-Related Apoptosis-Inducing Ligand / metabolism* |
| IF | 42.779 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 332 |
| Altmetric score changes over past 6months | 7.0 |
| Resource | |
| Mice | RBRC05737 |