小柯机器人

美国国立卫生研究院Ronald N. Germain、Anita Gola等研究人员合作发现，共生驱动的肝脏免疫分区促进宿主防御。相关论文于2020年11月25日在线发表在《自然》杂志上。

Title: Commensal-driven immune zonation of the liver promotes host defence

Author: Anita Gola, Michael G. Dorrington, Emily Speranza, Claudia Sala, Rochelle M. Shih, Andrea J. Radtke, Harikesh S. Wong, Antonio P. Baptista, Jonathan M. Hernandez, Gastone Castellani, Iain D. C. Fraser, Ronald N. Germain

Issue&Volume: 2020-11-25

Abstract: The liver connects the intestinal portal vasculature with the general circulation, using a diverse array of immune cells to protect from pathogens that translocate from the gut1. In liver lobules, blood flows from portal triads that are situated in periportal lobular regions to the central vein via a polarized sinusoidal network. Despite this asymmetry, resident immune cells in the liver are considered to be broadly dispersed across the lobule. This differs from lymphoid organs, in which immune cells adopt spatially biased positions to promote effective host defence2,3. Here we used quantitative multiplex imaging, genetic perturbations, transcriptomics, infection-based assays and mathematical modelling to reassess the relationship between the localization of immune cells in the liver and host protection. We found that myeloid and lymphoid resident immune cells concentrate around periportal regions. This asymmetric localization was not developmentally controlled, but resulted from sustained MYD88-dependent signalling induced by commensal bacteria in liver sinusoidal endothelial cells, which in turn regulated the composition of the pericellular matrix involved in the formation of chemokine gradients. In vivo experiments and modelling showed that this immune spatial polarization was more efficient than a uniform distribution in protecting against systemic bacterial dissemination. Together, these data reveal that liver sinusoidal endothelial cells sense the microbiome, actively orchestrating the localization of immune cells, to optimize host defence. The authors show that zonation extends to hepatic immune cells and that this spatial patterning is mediated by microbiome sensing by liver sinusoidal endothelial cells, and provide evidence that immune zonation is required to protect the host from the dissemination of blood-borne pathogens.

DOI: 10.1038/s41586-020-2977-2

Source: https://www.nature.com/articles/s41586-020-2977-2

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