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

被引：142

作者：

Bleriot, Camille ^{[1
,2
]}

Barreby, Emelie ^{[3
]}

Dunsmore, Garett ^{[2
]}

Ballaire, Raphaelle ^{[4
]}

Chakarov, Svetoslav ^{[1
,7
]}

Ficht, Xenia ^{[5
]}

De Simone, Giorgia ^{[5
,6
]}

Andreata, Francesco ^{[5
]}

Fumagalli, Valeria ^{[5
,6
]}

Guo, Wei ^{[7
]}

Wan, Guochen ^{[1
]}

Gessain, Gregoire ^{[1
]}

Khalilnezhad, Ahad ^{[1
,8
]}

Zhang, Xiao Meng ^{[1
]}

Ang, Nicholas ^{[1
]}

Chen, Ping ^{[3
]}

Morgantini, Cecilia ^{[3
]}

Azzimato, Valerio ^{[3
]}

Kong, Wan Ting ^{[1
]}

Liu, Zhaoyuan ^{[7
]}

Pai, Rhea ^{[9
]}

Lum, Josephine ^{[1
]}

Shihui, Foo ^{[1
]}

Low, Ivy ^{[1
]}

Xu, Connie ^{[3
]}

Malleret, Benoit ^{[1
,8
]}

Kairi, Muhammad Faris Mohd ^{[1
]}

Balachander, Akhila ^{[1
]}

Cexus, Olivier ^{[10
]}

Larbi, Anis ^{[1
]}

Lee, Bernett ^{[1
]}

Newell, Evan W. ^{[1
]}

Ng, Lai Guan ^{[1
,8
]}

Phoo, Wint Wint ^{[11
]}

Sobota, Radoslaw M. ^{[11
]}

Sharma, Ankur ^{[9
]}

Howland, Shanshan W. ^{[1
]}

Chen, Jinmiao ^{[1
]}

Bajenoff, Marc ^{[12
]}

Yvan-Charvet, Laurent ^{[13
]}

Venteclef, Nicolas ^{[14
]}

Iannacone, Matteo ^{[5
,6
,15
]}

Aouadi, Myriam ^{[3
]}

Ginhoux, Florent ^{[1
,7
,8
,16
]}

机构：

[1] ASTAR, Singapore Immunol Network SIgN, Singapore 138648, Singapore

[2] Gustave Roussy, INSERM, U1015, F-94800 Villejuif, France

[3] Karolinska Inst, Ctr Infect Med, Dept Med, S-14157 Huddinge, Sweden

[4] Inovarion, F-75005 Paris, France

[5] IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy

[6] Univ Vita Salute San Raffaele, I-20132 Milan, Italy

[7] Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Sch Med, Shanghai 200025, Peoples R China

[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Life Sci Inst,Immunol Program, Dept Microbiol & Immunol,Immunol Translat Res Pro, Singapore 117543, Singapore

[9] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore

[10] Univ Surrey, Fac Hlth & Med Sci, Biosci & Med, Guildford GU2 7XH, Surrey, England

[11] ASTAR, Inst Mol & Cell Biol, SingMass Natl Lab, Funct Prote Lab, Singapore 138673, Singapore

[12] Aix Marseille Univ, CIML, INSERM, CNRS, F-13288 Marseille, France

[13] UMR INSERM U1065 UNS, C3M, F-06204 Nice, France

[14] Univ Paris, Sorbonne Univ, Ctr Rech Cordeliers, INSERM,IMMEDIAB Lab, F-75006 Paris, France

[15] IRCCS San Raffaele Sci Inst, Expt Imaging Ctr, I-20132 Milan, Italy

[16] SingHlth Duke NUS Acad Med Ctr, Translat Immunol Inst, Singapore 169856, Singapore

来源：

IMMUNITY | 2021年 / 54卷 / 09期

基金：

欧洲研究理事会;

关键词：

LIVER MACROPHAGES; GLOBAL EPIDEMIOLOGY; INSULIN SENSITIVITY; MYELOID CELLS; RNA-SEQ; HETEROGENEITY; MONOCYTES; PREVALENCE; LANDSCAPE; NETWORK;

D O I：

10.1016/j.immuni.2021.08.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 CD206(lo)ESAM(-) population (KC1) and a minor CD206(hi)ESAM(+) 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.

引用

页码：2101 / +

页数：22

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