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A subset of Kupffer cells regulates metabolism through the expression of CD36
Open accessAbstract
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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“This may also have more direct consequences for metabolic injury in hepatocytes, since KCs, or at least their CD206+ESAM+ subset, actively participate in lipid metabolism.77”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [77]
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“A series of elegant studies using single-cell RNA sequencing (scRNA-seq) has provided insights into hepatic immune cell heterogeneity that are unprecedented in their detail, revealing striking alterations, particularly in myeloid cells and macrophages in NAFLD,55–60”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [56]
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“Kupffer cells comprise subsets/differentiation states, of which the CD206hi ESAM+ subtype (in mice) participates in fatty acid metabolism and may thereby directly drive NASH.56”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [56]
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Metadata
- 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)
- 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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