新加坡A∗STAR研究所Florent Ginhoux、Camille Blériot等研究人员合作发现，一个库普弗细胞的亚群通过表达CD36调节代谢。相关论文于2021年8月31日在线发表在《免疫》杂志上。

研究人员使用高维方法来描述了小鼠肝脏中巨噬细胞群的特征。研究人员在胚胎衍生的库普弗细胞（KC）中发现了两个不同的群体，它们共享一个核心特征，同时不同地表达许多基因和蛋白质：一个主要的CD206^lo ESAM^-群体（KC1）和一个次要的CD206^hi ESAM⁺群体（KC2）。KC2表达参与代谢过程的基因，包括稳态和饮食诱导的肥胖和肝脏脂肪变性中的脂肪酸代谢。通过耗尽KC2或靶向沉默脂肪酸转运体Cd36的功能实验揭示了KC2在与肥胖相关肝脏氧化应激中的重要贡献。总之，这项研究显示，KC的异质性比预期的要高，特别是描述了一个具有代谢功能的亚群。

据了解，组织巨噬细胞是免疫细胞，其表型和功能是由起源和微环境决定的。然而，组织是复杂的环境，同一器官内巨噬细胞的异质性至今被忽视。

附：英文原文

Title: A subset of Kupffer cells regulates metabolism through the expression of CD36

Author: Camille Blériot, Emelie Barreby, Garett Dunsmore, Raphaelle Ballaire, Svetoslav Chakarov, Xenia Ficht, Giorgia De Simone, Francesco Andreata, Valeria Fumagalli, Wei Guo, Guochen Wan, Gregoire Gessain, Ahad Khalilnezhad, Xiao Meng Zhang, Nicholas Ang, Ping Chen, Cecilia Morgantini, Valerio Azzimato, Wan Ting Kong, Zhaoyuan Liu, Rhea Pai, Josephine Lum, Foo Shihui, Ivy Low, Connie Xu, Benoit Malleret, Muhammad Faris Mohd Kairi, Akhila Balachander, Olivier Cexus, Anis Larbi, Bernett Lee, Evan W. Newell, Lai Guan Ng, Wint Wint Phoo, Radoslaw M. Sobota, Ankur Sharma, Shanshan W. Howland, Jinmiao Chen, Marc Bajenoff, Laurent Yvan-Charvet, Nicolas Venteclef, Matteo Iannacone, Myriam Aouadi, Florent Ginhoux

Issue&Volume: 2021-08-31

Abstract: Tissue macrophages are immune cells whose phenotypes and functions are dictated byorigin and niches. However, tissues are complex environments, and macrophage heterogeneitywithin the same organ has been overlooked so far. Here, we used high-dimensional approachesto characterize macrophage populations in the murine liver. We identified two distinctpopulations among embryonically derived Kupffer cells (KCs) sharing a core signaturewhile differentially expressing numerous genes and proteins: a major CD206loESAM– population (KC1) and a minor CD206hiESAM+ population (KC2). KC2 expressed genes involved in metabolic processes, includingfatty acid metabolism both in steady-state and in diet-induced obesity and hepaticsteatosis. Functional characterization by depletion of KC2 or targeted silencing ofthe fatty acid transporter Cd36 highlighted a crucial contribution of KC2 in the liver oxidative stress associatedwith obesity. In summary, our study reveals that KCs are more heterogeneous than anticipated,notably describing a subpopulation wired with metabolic functions.

DOI: 10.1016/j.immuni.2021.08.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00336-8