A subset of Kupffer cells regulates metabolism through the expression of CD36.

Abstract

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

• Authors: 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
• Journal: Immunity (Immunity) Vol. 54 Issue 9 Pg. 2101-2116.e6 (09 14 2021) ISSN: 1097-4180 [Electronic] United States
• PMID: 34469775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• CD36 Antigens

Topics

• Animals
• CD36 Antigens (metabolism)
• Kupffer Cells (metabolism)
• Liver (metabolism)
• Mice
• Obesity (metabolism)
• Oxidative Stress (physiology)