美国哈佛医学院Francisco J. Quintana团队取得一项新突破。他们发现肠道许可的IFNγ+ NK细胞驱动LAMP1 + TRAIL +抗炎性星形胶质细胞。相关论文发表在2021年1月6日出版的《自然》杂志上。
他们使用高通量流式细胞术筛选，单细胞RNA测序和基于CRISPR–Cas9的细胞特异性体内遗传扰动，他们在小鼠中鉴定了表达溶酶体蛋白LAMP12和死亡受体配体TRAIL3的星形胶质细胞的一个亚群。LAMP1 + TRAIL +星形胶质细胞通过TRAIL-DR5信号传导诱导T细胞凋亡，从而限制了中枢神经系统的炎症。
在体内平衡条件下，星形胶质细胞杀伤细胞中干扰素-γ（IFNγ）的表达是由肠道微生物组调节的，干扰素-γ（IFNγ）驱动星形胶质细胞中TRAIL的表达。在炎症的情况下，T细胞和小胶质细胞产生的分子抑制星形胶质细胞中的TRAIL表达。
总之，他们显示LAMP1 + TRAIL +星形胶质细胞通过诱导T细胞凋亡来限制中枢神经系统（CNS）炎症，并且该星形胶质细胞亚群由微生物组许可的脑膜IFNγ+ NK细胞维持。
据了解，星形胶质细胞是在CNS中丰富的胶质细胞，具有重要的体内平衡和促进疾病的功能。然而，关于星形胶质细胞的稳态抗炎活性及其调节知之甚少。
附：英文原文
Title: Gut-licensed IFNγ + NK cells drive LAMP1 + TRAIL + anti-inflammatory astrocytes
Author: Liliana M. Sanmarco, Michael A. Wheeler, Cristina Gutirrez-Vzquez, 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
Issue&Volume: 2021-01-06
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.
DOI: 10.1038/s41586-020-03116-4
Source: https://www.nature.com/articles/s41586-020-03116-4
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
