Brown adipose tissue monocytes support tissue expansion

Alexandre Gallerand; Marion I. Stunault; Johanna Merlin; Hannah P. Luehmann; Deborah H. Sultan; Maria M. Firulyova; Virginie Magnone; Narges Khedher; Antoine Jalil; Bastien Dolfi; Alexia Castiglione; Adelie Dumont; Marion Ayrault; Nathalie Vaillant; Jérôme Gilleron; Pascal Barbry; David Dombrowicz; Matthias Mack; David Masson; Thomas Bertero; Burkhard Becher; Jesse W. Williams; Konstantin Zaitsev; Yongjian Liu; Rodolphe R. Guinamard; Laurent Yvan-Charvet; Stoyan Ivanov

doi:10.1038/s41467-021-25616-1

Brown adipose tissue monocytes support tissue expansion

Alexandre Gallerand, Marion I. Stunault, Johanna Merlin, Hannah P. Luehmann, Deborah H. Sultan, Maria M. Firulyova, Virginie Magnone, Narges Khedher, Antoine Jalil, Bastien Dolfi, Alexia Castiglione, Adelie Dumont, Marion Ayrault, Nathalie Vaillant, Jérôme Gilleron, Pascal Barbry, David Dombrowicz, Matthias Mack, David Masson, Thomas BerteroBurkhard Becher, Jesse W. Williams, Konstantin Zaitsev, Yongjian Liu, Rodolphe R. Guinamard, Laurent Yvan-Charvet, Stoyan Ivanov

Physiology

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36 Scopus citations

Abstract

Monocytes are part of the mononuclear phagocytic system. Monocytes play a central role during inflammatory conditions and a better understanding of their dynamics might open therapeutic opportunities. In the present study, we focused on the characterization and impact of monocytes on brown adipose tissue (BAT) functions during tissue remodeling. Single-cell RNA sequencing analysis of BAT immune cells uncovered a large diversity in monocyte and macrophage populations. Fate-mapping experiments demonstrated that the BAT macrophage pool requires constant replenishment from monocytes. Using a genetic model of BAT expansion, we found that brown fat monocyte numbers were selectively increased in this scenario. This observation was confirmed using a CCR2-binding radiotracer and positron emission tomography. Importantly, in line with their tissue recruitment, blood monocyte counts were decreased while bone marrow hematopoiesis was not affected. Monocyte depletion prevented brown adipose tissue expansion and altered its architecture. Podoplanin engagement is strictly required for BAT expansion. Together, these data redefine the diversity of immune cells in the BAT and emphasize the role of monocyte recruitment for tissue remodeling.

Original language	English (US)
Article number	5255
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25616-1
State	Published - Dec 1 2021

Bibliographical note

Funding Information:
We would like to thank Dr Pierre Leclère for the helpful discussions. We would like to thank Jean-Paul Pais de Barros from the Lipidomic Analytic platform (LAP) of the University of Burgundy for technical support. We thank the C3M Animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie Côte d’Azur (MICA), and particularly the imaging site of C3M (INSERM U1065) supported by Conseil Régional, Conseil Départemental, and IBISA. We sincerely thank Maéva Gesson and Marie Irondelle for their help. We acknowledge the flow cytometry facility from the «Institut de Pharmacologie Moléculaire et Cellulaire», part of the MICA GIS IBiSA labeled platform, and we thank Julie Cazareth for her help. We thank Dr. Jean-François Tanti for sharing Ucp1Cre mice and Dr. Stephan Clavel for sharing MEFs. A.G. is supported by the French government, through the UCAJedi Investments in the Future projects managed by the National Research Agency (ANR) (ANR-15-IDEX-01). T.B. is supported by Agence Nationale de la Recherche (ANR-18-CE14-0025 and ANR-20-CE14-0006-02). M.F. and K.Z. were supported by the Government of Russian Federation (Grant 08-08). R.R.G. is supported by Center National de la Recherche Scientifique (CNRS). D.D. was supported by grants from the ANR and the European Union: EGID ANR-10-LABX-46. J.W.W. was supported by the National Institutes of Health (NIH) grant HL138163. L.Y.C. is supported by Institut National de la Sante et de la Recherche Medicale (INSERM), Fondation de France (00066474), and the European Research Council (ERC) consolidator program (ERC2016COG724838). S.I. is supported by Institut National de la Sante et de la Recherche Medicale (INSERM) and Agence Nationale de la Recherche (ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01).

Publisher Copyright:
© 2021, The Author(s).

Keywords

Adiponectin/genetics
Adipose Tissue, Brown/cytology
Animals
Cell Differentiation/genetics
Leukocyte Count
Macrophages/cytology
Membrane Glycoproteins/metabolism
Mice, Transgenic
Monocytes/cytology
Positron-Emission Tomography
Receptors, CCR2/genetics

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article

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10.1038/s41467-021-25616-1

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Gallerand, A., Stunault, M. I., Merlin, J., Luehmann, H. P., Sultan, D. H., Firulyova, M. M., Magnone, V., Khedher, N., Jalil, A., Dolfi, B., Castiglione, A., Dumont, A., Ayrault, M., Vaillant, N., Gilleron, J., Barbry, P., Dombrowicz, D., Mack, M., Masson, D., ... Ivanov, S. (2021). Brown adipose tissue monocytes support tissue expansion. Nature communications, 12(1), Article 5255. https://doi.org/10.1038/s41467-021-25616-1

Gallerand, A, Stunault, MI, Merlin, J, Luehmann, HP, Sultan, DH, Firulyova, MM, Magnone, V, Khedher, N, Jalil, A, Dolfi, B, Castiglione, A, Dumont, A, Ayrault, M, Vaillant, N, Gilleron, J, Barbry, P, Dombrowicz, D, Mack, M, Masson, D, Bertero, T, Becher, B, Williams, JW, Zaitsev, K, Liu, Y, Guinamard, RR, Yvan-Charvet, L & Ivanov, S 2021, 'Brown adipose tissue monocytes support tissue expansion', Nature communications, vol. 12, no. 1, 5255. https://doi.org/10.1038/s41467-021-25616-1

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title = "Brown adipose tissue monocytes support tissue expansion",

abstract = "Monocytes are part of the mononuclear phagocytic system. Monocytes play a central role during inflammatory conditions and a better understanding of their dynamics might open therapeutic opportunities. In the present study, we focused on the characterization and impact of monocytes on brown adipose tissue (BAT) functions during tissue remodeling. Single-cell RNA sequencing analysis of BAT immune cells uncovered a large diversity in monocyte and macrophage populations. Fate-mapping experiments demonstrated that the BAT macrophage pool requires constant replenishment from monocytes. Using a genetic model of BAT expansion, we found that brown fat monocyte numbers were selectively increased in this scenario. This observation was confirmed using a CCR2-binding radiotracer and positron emission tomography. Importantly, in line with their tissue recruitment, blood monocyte counts were decreased while bone marrow hematopoiesis was not affected. Monocyte depletion prevented brown adipose tissue expansion and altered its architecture. Podoplanin engagement is strictly required for BAT expansion. Together, these data redefine the diversity of immune cells in the BAT and emphasize the role of monocyte recruitment for tissue remodeling.",

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author = "Alexandre Gallerand and Stunault, {Marion I.} and Johanna Merlin and Luehmann, {Hannah P.} and Sultan, {Deborah H.} and Firulyova, {Maria M.} and Virginie Magnone and Narges Khedher and Antoine Jalil and Bastien Dolfi and Alexia Castiglione and Adelie Dumont and Marion Ayrault and Nathalie Vaillant and J{\'e}r{\^o}me Gilleron and Pascal Barbry and David Dombrowicz and Matthias Mack and David Masson and Thomas Bertero and Burkhard Becher and Williams, {Jesse W.} and Konstantin Zaitsev and Yongjian Liu and Guinamard, {Rodolphe R.} and Laurent Yvan-Charvet and Stoyan Ivanov",

note = "Funding Information: We would like to thank Dr Pierre Lecl{\`e}re for the helpful discussions. We would like to thank Jean-Paul Pais de Barros from the Lipidomic Analytic platform (LAP) of the University of Burgundy for technical support. We thank the C3M Animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie C{\^o}te d{\textquoteright}Azur (MICA), and particularly the imaging site of C3M (INSERM U1065) supported by Conseil R{\'e}gional, Conseil D{\'e}partemental, and IBISA. We sincerely thank Ma{\'e}va Gesson and Marie Irondelle for their help. We acknowledge the flow cytometry facility from the «Institut de Pharmacologie Mol{\'e}culaire et Cellulaire», part of the MICA GIS IBiSA labeled platform, and we thank Julie Cazareth for her help. We thank Dr. Jean-Fran{\c c}ois Tanti for sharing Ucp1Cre mice and Dr. Stephan Clavel for sharing MEFs. A.G. is supported by the French government, through the UCAJedi Investments in the Future projects managed by the National Research Agency (ANR) (ANR-15-IDEX-01). T.B. is supported by Agence Nationale de la Recherche (ANR-18-CE14-0025 and ANR-20-CE14-0006-02). M.F. and K.Z. were supported by the Government of Russian Federation (Grant 08-08). R.R.G. is supported by Center National de la Recherche Scientifique (CNRS). D.D. was supported by grants from the ANR and the European Union: EGID ANR-10-LABX-46. J.W.W. was supported by the National Institutes of Health (NIH) grant HL138163. L.Y.C. is supported by Institut National de la Sante et de la Recherche Medicale (INSERM), Fondation de France (00066474), and the European Research Council (ERC) consolidator program (ERC2016COG724838). S.I. is supported by Institut National de la Sante et de la Recherche Medicale (INSERM) and Agence Nationale de la Recherche (ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41467-021-25616-1",

language = "English (US)",

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T1 - Brown adipose tissue monocytes support tissue expansion

AU - Gallerand, Alexandre

AU - Stunault, Marion I.

AU - Merlin, Johanna

AU - Luehmann, Hannah P.

AU - Sultan, Deborah H.

AU - Firulyova, Maria M.

AU - Magnone, Virginie

AU - Khedher, Narges

AU - Jalil, Antoine

AU - Dolfi, Bastien

AU - Castiglione, Alexia

AU - Dumont, Adelie

AU - Ayrault, Marion

AU - Vaillant, Nathalie

AU - Gilleron, Jérôme

AU - Barbry, Pascal

AU - Dombrowicz, David

AU - Mack, Matthias

AU - Masson, David

AU - Bertero, Thomas

AU - Becher, Burkhard

AU - Williams, Jesse W.

AU - Zaitsev, Konstantin

AU - Liu, Yongjian

AU - Guinamard, Rodolphe R.

AU - Yvan-Charvet, Laurent

AU - Ivanov, Stoyan

N1 - Funding Information: We would like to thank Dr Pierre Leclère for the helpful discussions. We would like to thank Jean-Paul Pais de Barros from the Lipidomic Analytic platform (LAP) of the University of Burgundy for technical support. We thank the C3M Animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie Côte d’Azur (MICA), and particularly the imaging site of C3M (INSERM U1065) supported by Conseil Régional, Conseil Départemental, and IBISA. We sincerely thank Maéva Gesson and Marie Irondelle for their help. We acknowledge the flow cytometry facility from the «Institut de Pharmacologie Moléculaire et Cellulaire», part of the MICA GIS IBiSA labeled platform, and we thank Julie Cazareth for her help. We thank Dr. Jean-François Tanti for sharing Ucp1Cre mice and Dr. Stephan Clavel for sharing MEFs. A.G. is supported by the French government, through the UCAJedi Investments in the Future projects managed by the National Research Agency (ANR) (ANR-15-IDEX-01). T.B. is supported by Agence Nationale de la Recherche (ANR-18-CE14-0025 and ANR-20-CE14-0006-02). M.F. and K.Z. were supported by the Government of Russian Federation (Grant 08-08). R.R.G. is supported by Center National de la Recherche Scientifique (CNRS). D.D. was supported by grants from the ANR and the European Union: EGID ANR-10-LABX-46. J.W.W. was supported by the National Institutes of Health (NIH) grant HL138163. L.Y.C. is supported by Institut National de la Sante et de la Recherche Medicale (INSERM), Fondation de France (00066474), and the European Research Council (ERC) consolidator program (ERC2016COG724838). S.I. is supported by Institut National de la Sante et de la Recherche Medicale (INSERM) and Agence Nationale de la Recherche (ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01). Publisher Copyright: © 2021, The Author(s).

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Monocytes are part of the mononuclear phagocytic system. Monocytes play a central role during inflammatory conditions and a better understanding of their dynamics might open therapeutic opportunities. In the present study, we focused on the characterization and impact of monocytes on brown adipose tissue (BAT) functions during tissue remodeling. Single-cell RNA sequencing analysis of BAT immune cells uncovered a large diversity in monocyte and macrophage populations. Fate-mapping experiments demonstrated that the BAT macrophage pool requires constant replenishment from monocytes. Using a genetic model of BAT expansion, we found that brown fat monocyte numbers were selectively increased in this scenario. This observation was confirmed using a CCR2-binding radiotracer and positron emission tomography. Importantly, in line with their tissue recruitment, blood monocyte counts were decreased while bone marrow hematopoiesis was not affected. Monocyte depletion prevented brown adipose tissue expansion and altered its architecture. Podoplanin engagement is strictly required for BAT expansion. Together, these data redefine the diversity of immune cells in the BAT and emphasize the role of monocyte recruitment for tissue remodeling.

AB - Monocytes are part of the mononuclear phagocytic system. Monocytes play a central role during inflammatory conditions and a better understanding of their dynamics might open therapeutic opportunities. In the present study, we focused on the characterization and impact of monocytes on brown adipose tissue (BAT) functions during tissue remodeling. Single-cell RNA sequencing analysis of BAT immune cells uncovered a large diversity in monocyte and macrophage populations. Fate-mapping experiments demonstrated that the BAT macrophage pool requires constant replenishment from monocytes. Using a genetic model of BAT expansion, we found that brown fat monocyte numbers were selectively increased in this scenario. This observation was confirmed using a CCR2-binding radiotracer and positron emission tomography. Importantly, in line with their tissue recruitment, blood monocyte counts were decreased while bone marrow hematopoiesis was not affected. Monocyte depletion prevented brown adipose tissue expansion and altered its architecture. Podoplanin engagement is strictly required for BAT expansion. Together, these data redefine the diversity of immune cells in the BAT and emphasize the role of monocyte recruitment for tissue remodeling.

KW - Adiponectin/genetics

KW - Adipose Tissue, Brown/cytology

KW - Animals

KW - Cell Differentiation/genetics

KW - Leukocyte Count

KW - Macrophages/cytology

KW - Membrane Glycoproteins/metabolism

KW - Mice, Transgenic

KW - Monocytes/cytology

KW - Positron-Emission Tomography

KW - Receptors, CCR2/genetics

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DO - 10.1038/s41467-021-25616-1

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SN - 2041-1723

VL - 12

JO - Nature communications

JF - Nature communications

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ER -

Brown adipose tissue monocytes support tissue expansion

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

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