Brown adipose tissue monocytes support tissue expansion

• DOI: 10.1038/s41467-021-25616-1
• Publication Date: 2021-09-06T10:04:08Z
• Authors: 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. Guina...; Laurent Yvan-Charvet; Stoyan Ivanov
• Keywords: Membrane Glycoproteins; Receptors, CCR2; [SDV]Life Sciences [q-bio]; Science; Macrophages; Q; 610 Medicine & health; 1600 General Chemistry; Cell Differentiation; Mice, Transgenic; 10263 Institute of Experimental Immunology; 3100 General Physics and Astronomy; Article; Monocytes; [SDV] Life Sciences [q-bio]; Leukocyte Count; Adipose Tissue, Brown; 1300 General Biochemistry, Genetics and Molecular Biology; Positron-Emission Tomography; 570 Life sciences; biology; Animals; Adiponectin

AbstractMonocytes 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.