Nature:肠道菌群“训练”的免疫细胞,帮助大脑抗炎症
创作:mildbreeze 审核:mildbreeze 02月01日
  • 在小鼠中鉴定出一类星形胶质细胞,表达溶酶体蛋白LAMP1和死亡受体配体TRAIL;
  • 这类细胞通过TRAIL-DR5信号诱导效应T细胞凋亡,从而限制大脑炎症;
  • 在炎症状态下,T细胞和小胶质细胞产生的促炎细胞因子,会抑制星形胶质细胞表达TRAIL;
  • 在稳态状态下,脑膜处的自然杀伤(NK)细胞产生IFNγ,能驱动星形胶质细胞表达TRAIL;
  • 肠道菌群激活NK细胞表达IFNγ,这些IFNγ+ NK细胞迁移至脑膜诱导产生抗炎的星形胶质细胞。
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mildbreeze
星形胶质细胞是大脑中大量存在的一类神经胶质细胞,对大脑健康有重要作用。Nature最新发表的一项研究鉴定出一类LAMP1+ TRAIL+ 星形胶质细胞,能通过TRAIL介导的促炎T细胞凋亡来限制大脑炎症。进一步研究表明,由肠道菌群“训练”并迁移至脑膜的产IFNγ的NK细胞,能有效诱导星形胶质细胞表达TRAIL,发挥抗炎作用。此前有研究发现,源于肠道的IgA+ B细胞能迁移至大脑,通过产生抗炎细胞因子IL10来抑制大脑炎症(查看文章);这篇在Nature发表的最新研究再次表明,免疫细胞的迁移是肠-脑轴中的一大要素。总之,这项研究揭示了肠道菌群影响大脑炎症的一种新机制,并为调节星形胶质细胞以治疗多发性硬化等神经疾病,提供了新靶点。
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Nature [IF:42.778]

Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes

肠道许可的IFNγ+ NK细胞驱动LAMP1+TRAIL+抗炎星形胶质细胞

10.1038/s41586-020-03116-4

01-06, Article

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Abstract:收起
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.

First Authors:
Liliana M Sanmarco,Michael A Wheeler

Correspondence Authors:
Francisco J Quintana

All Authors:
Liliana M Sanmarco,Michael A Wheeler,Cristina Gutiérrez-Vázquez,Carolina Manganeli Polonio,Mathias Linnerbauer,Felipe A Pinho-Ribeiro,Zhaorong Li,Federico Giovannoni,Katelyn V Batterman,Giulia Scalisi,Stephanie E J Zandee,Evelyn S Heck,Moneera Alsuwailm,Douglas L Rosene,Burkhard Becher,Isaac M Chiu,Alexandre Prat,Francisco J Quintana

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Science Signaling期刊

A TRAIL from gut to brain

2021-02-23

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