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.
Bibliographical noteFunding 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).
© 2021, The Author(s).