Cited by 236Immune cells in cancerLiver physiology and pathologyAdipokines, Inflammation, and Metabolic Diseases

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

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Blériot, Camille, Barreby, Emelie, Dunsmore, Garett, Ballaire, Raphaelle, Chakarov, Svetoslav, Ficht, Xenia, De Simone, Giorgia, Andreata, Francesco, Fumagalli, Valeria, Guo, Wei, Wan, Guochen, Gessain, Gregoire, Khalilnezhad, Ahad, Zhang, Xiao Meng, Ang, Nicholas, Chen, Ping, Morgantini, Cecilia, Azzimato, Valerio, Kong, Wan Ting, Liu, Zhaoyuan, Pai, Rhea, Lum, Josephine, Shihui, Foo, Low, Ivy, Xu, Connie, Malleret, Benoit, Kairi, Muhammad Faris Mohd, Balachander, Akhila, Cexus, Olivier, Larbi, Anis, Lee, Bernett, Newell, Evan W., Ng, Lai Guan, Phoo, Wint Wint, Sobota, Radoslaw M., Sharma, Ankur, Howland, Shanshan W., Chen, Jinmiao, Bajenoff, Marc, Yvan-Charvet, Laurent, Venteclef, Nicolas, Iannacone, Matteo, Aouadi, Myriam, Ginhoux, Florent·2021·Immunity

DOI 10.1016/j.immuni.2021.08.006

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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 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.

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Authors: Blériot, C., Barreby, E., Dunsmore, G., Ballaire, R., Chakarov, S., Ficht, X., De Simone, G., Andreata, F., Fumagalli, V., Guo, W., Wan, G., Gessain, G., Khalilnezhad, A., Zhang, X. M., Ang, N., Chen, P., Morgantini, C., Azzimato, V., Kong, W. T., Liu, Z., Pai, R., Lum, J., Shihui, F., Low, I., Xu, C., Malleret, B., Kairi, M. F. M., Balachander, A., Cexus, O., Larbi, A., Lee, B., Newell, E. W., Ng, L. G., Phoo, W. W., Sobota, R. M., Sharma, A., Howland, S. W., Chen, J., Bajenoff, M., Yvan-Charvet, L., Venteclef, N., Iannacone, M., Aouadi, M., & Ginhoux, F.
Affiliations: Agency for Science, Technology and Research (SG)
Karolinska Institutet (SE)
Inserm (FR)
IRCCS Ospedale San Raffaele (IT)
Vita-Salute San Raffaele University (IT)
Shanghai Jiao Tong University (CN)
Genome Institute of Singapore (SG)
University of Surrey (GB)
Corresponding author: Blériot, Camille
Ginhoux, Florent
ORCID: Blériot, Camille
Barreby, Emelie
Dunsmore, Garett
Chakarov, Svetoslav
Ficht, Xenia
Andreata, Francesco
Fumagalli, Valeria
Guo, Wei
Khalilnezhad, Ahad
Zhang, Xiao Meng
Ang, Nicholas
Chen, Ping
Morgantini, Cecilia
Azzimato, Valerio
Kong, Wan Ting
Liu, Zhaoyuan
Lum, Josephine
Low, Ivy
Xu, Connie
Balachander, Akhila
Cexus, Olivier
Larbi, Anis
Lee, Bernett
Newell, Evan W.
Ng, Lai Guan
Phoo, Wint Wint
Sobota, Radoslaw M.
Sharma, Ankur
Howland, Shanshan W.
Chen, Jinmiao
Venteclef, Nicolas
Iannacone, Matteo
Aouadi, Myriam
Ginhoux, Florent
Venue: Immunity
Publisher: Elsevier BV
Published: 2021-09
Volume: 54
Issue: 9
Pages: 2101-2116.e6
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2021.08.006
OpenAlex: W3198090726
Cited by: 236
References: 84
Citations by year: 2026: 35 · 2025: 56 · 2024: 51 · 2023: 59 · 2022: 31 · 2021: 4
FWCI: 13.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
BOA (University of Milano-Bicocca) (submittedVersion, other-oa)
Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Funders: Agency for Science, Technology and Research (NUHSRO/ 2018/006/SU/01, NRFI2017-02)
Biomedical Research Council (IAF311006, H16/99/b0/011, 16/99/b0/011)
Horizon 2020 Framework Programme (ERC-EpiFAT 725790, 864788)
European Molecular Biology Organization
European Research Council
Horizon 2020
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: Kupffer cells, CD36, fatty acid metabolism, macrophage heterogeneity, hepatic macrophages, CD206, ESAM, diet-induced obesity, hepatic steatosis, oxidative stress
MeSH terms: Animals, Kupffer Cells, Liver, Obesity, Oxidative Stress, CD36 Antigens, Mice

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

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