CD226+adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism

Macrophages are innate immune cells present in all tissues, in which they participate in immune responses and maintenance of tissue homeostasis. They develop either from embryonic precursors or from circulating monocytes, and their origin impacts their functions. We previously observed robust recruitment of monocytes to brown adipose tissue in which they could differentiation into two distinct macrophage subsets identifiable by CD206 or CD226 expression. In the present study, we investigated monocyte differentiation pathways in brown adipose tissue and the function of monocyte-derived macrophages. Fate mapping analysis revealed a low contribution of GMP- and a high contribution of MDP-derived monocytes to the CD226 high macrophage subset. Importantly, adoptive transfer experiments demonstrate that MDP- but not GMP-derived monocytes are pre-conditioned to give rise to CD226 high macrophages. We found that MDP-derived CD226 high macrophages were also present in other tissues including peritoneal cavity, adrenal glands and all adipose depots. CD226 high macrophages were regulated by both GM-CSF and CSF1R. Genetic depletion of CD226 high macrophages caused increased BAT and plasma triglyceride content. We thus identify CD226 high MDP-derived macrophages as a new myeloid cell type conserved across tissues and tied to lipid metabolism homeostasis.