TY - JOUR
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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85114646351&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114646351&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-25616-1
DO - 10.1038/s41467-021-25616-1
M3 - Article
C2 - 34489438
AN - SCOPUS:85114646351
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5255
ER -