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

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

doi:10.1016/j.immuni.2021.08.006

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

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 LiuRhea 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

Research output: Contribution to journal › Article › peer-review

111 Citations (Scopus)

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^loESAM^– population (KC1) and a minor CD206^hiESAM⁺ 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.

Original language	English
Pages (from-to)	2101-2116.e6
Journal	Immunity
Volume	54
Issue number	9
DOIs	https://doi.org/10.1016/j.immuni.2021.08.006
Publication status	Published - 14 Sept 2021
Externally published	Yes

Keywords

CD206
CD36
Kupffer cells
heterogeneity
high fat diet
liver
macrophages
metabolism
scRNA-seq
single cell

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10.1016/j.immuni.2021.08.006

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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., ... Ginhoux, F. (2021). A subset of Kupffer cells regulates metabolism through the expression of CD36. Immunity, 54(9), 2101-2116.e6. https://doi.org/10.1016/j.immuni.2021.08.006

@article{132a69b64d0f4fdc8892206a69c2b4e7,

title = "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.",

keywords = "CD206, CD36, Kupffer cells, heterogeneity, high fat diet, liver, macrophages, metabolism, scRNA-seq, single cell",

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

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = sep,

day = "14",

doi = "10.1016/j.immuni.2021.08.006",

language = "English",

volume = "54",

pages = "2101--2116.e6",

journal = "Immunity",

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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, XM, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, WT, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, MFM, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, EW, Ng, LG, Phoo, WW, Sobota, RM, Sharma, A, Howland, SW, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M & Ginhoux, F 2021, 'A subset of Kupffer cells regulates metabolism through the expression of CD36', Immunity, vol. 54, no. 9, pp. 2101-2116.e6. https://doi.org/10.1016/j.immuni.2021.08.006

TY - JOUR

T1 - A subset of Kupffer cells regulates metabolism through the expression of CD36

AU - Blériot, Camille

AU - Barreby, Emelie

AU - Dunsmore, Garett

AU - Ballaire, Raphaelle

AU - Chakarov, Svetoslav

AU - Ficht, Xenia

AU - De Simone, Giorgia

AU - Andreata, Francesco

AU - Fumagalli, Valeria

AU - Guo, Wei

AU - Wan, Guochen

AU - Gessain, Gregoire

AU - Khalilnezhad, Ahad

AU - Zhang, Xiao Meng

AU - Ang, Nicholas

AU - Chen, Ping

AU - Morgantini, Cecilia

AU - Azzimato, Valerio

AU - Kong, Wan Ting

AU - Liu, Zhaoyuan

AU - Pai, Rhea

AU - Lum, Josephine

AU - Shihui, Foo

AU - Low, Ivy

AU - Xu, Connie

AU - Malleret, Benoit

AU - Kairi, Muhammad Faris Mohd

AU - Balachander, Akhila

AU - Cexus, Olivier

AU - Larbi, Anis

AU - Lee, Bernett

AU - Newell, Evan W.

AU - Ng, Lai Guan

AU - Phoo, Wint Wint

AU - Sobota, Radoslaw M.

AU - Sharma, Ankur

AU - Howland, Shanshan W.

AU - Chen, Jinmiao

AU - Bajenoff, Marc

AU - Yvan-Charvet, Laurent

AU - Venteclef, Nicolas

AU - Iannacone, Matteo

AU - Aouadi, Myriam

AU - Ginhoux, Florent

PY - 2021/9/14

Y1 - 2021/9/14

N2 - 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.

AB - 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.

KW - CD206

KW - CD36

KW - Kupffer cells

KW - heterogeneity

KW - high fat diet

KW - liver

KW - macrophages

KW - metabolism

KW - scRNA-seq

KW - single cell

UR - http://www.scopus.com/inward/record.url?scp=85116956756&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2021.08.006

DO - 10.1016/j.immuni.2021.08.006

M3 - Article

C2 - 34469775

AN - SCOPUS:85116956756

SN - 1074-7613

VL - 54

SP - 2101-2116.e6

JO - Immunity

JF - Immunity

IS - 9

ER -

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

Abstract

Keywords

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