英国伦敦弗朗西斯·克里克研究所Vassilis Pachnis、Fränze Progatzky研究团队发现肠道胶质细胞调控肠道免疫和组织修复。该研究于2021年10月20日发表于国际学术期刊《自然》杂志。
在本研究中，研究人员揭示了肠神经胶质细胞(EGC)在肠道稳态、免疫和组织修复中的重要作用。研究发现用Heligmosomoides polygyrus感染小鼠会导致肠神经胶质增生和干扰素γ(IFNγ)基因上调。炎症性肠病患者的EGC中也具有IFNγ依赖性基因模块上调。对肌层单细胞转录组学分析表明，胶质细胞特异性IFNγ信号缺失会导致全组织激活促炎转录程序。
此外，干扰素γ-EGC信号通路的破坏增强了肌层对蠕虫炎症和肉芽肿的反应。从机制上讲，Cxcl10的上调是EGC对IFNγ信号传导的早期即时反应，研究表明，这种趋化因子和肌膜中IFNγ信号传导下游的放大是对蠕虫炎症反应和肉芽肿消退所必需的。该研究表明，肠道胶质细胞中IFNγ信号的传导对肠道稳态至关重要，并揭示了IFN-EGC-CXCL10通路在感染攻击后免疫反应和组织修复中的关键作用。
据了解，组织维护和修复取决于多种细胞类型的协作。尽管上皮细胞、免疫细胞和基质细胞在肠道组织完整性中的作用已广为人知，但内在神经胶质网络的作用仍然未知。
附：英文原文
Title: Regulation of intestinal immunity and tissue repair by enteric glia
Author: Progatzky, Frnze, Shapiro, Michael, Chng, Song Hui, Garcia-Cassani, Bethania, Classon, Cajsa Helena, Sevgi, Selin, Laddach, Anna, Bon-Frauches, Ana Carina, Lasrado, Reena, Rahim, Maryam, Amaniti, Eleni-Maria, Boeing, Stefan, Shah, Kathleen, Entwistle, Lewis J., Surez-Bonnet, Alejandro, Wilson, Mark S., Stockinger, Brigitta, Pachnis, Vassilis
Issue&Volume: 2021-10-20
Abstract: Tissue maintenance and repair depend on the integrated activity of multiple cell types1. Whereas the contributions of epithelial2,3, immune4,5 and stromal cells6,7 in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here we uncover important roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We demonstrate that infection of mice with Heligmosomoides polygyrus leads to enteric gliosis and the upregulation of an interferon gamma (IFNγ) gene signature. IFNγ-dependent gene modules were also induced in EGCs from patients with inflammatory bowel disease8. Single-cell transcriptomics analysis of the tunica muscularis showed that glia-specific abrogation of IFNγ signalling leads to tissue-wide activation of pro-inflammatory transcriptional programs. Furthermore, disruption of the IFNγ–EGC signalling axis enhanced the inflammatory and granulomatous response of the tunica muscularis to helminths. Mechanistically, we show that the upregulation of Cxcl10 is an early immediate response of EGCs to IFNγ signalling and provide evidence that this chemokine and the downstream amplification of IFNγ signalling in the tunica muscularis are required for a measured inflammatory response to helminths and resolution of the granulomatous pathology. Our study demonstrates that IFNγ signalling in enteric glia is central to intestinal homeostasis and reveals critical roles of the IFNγ–EGC–CXCL10 axis in immune response and tissue repair after infectious challenge.
DOI: 10.1038/s41586-021-04006-z
Source: https://www.nature.com/articles/s41586-021-04006-z
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
