Université Côte d'Azur, INSERM, C3M, Nice, France.
Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.
Nat Commun. 2021 Sep 6;12(1):5255. doi: 10.1038/s41467-021-25616-1.
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.
单核细胞是单核吞噬细胞系统的一部分。单核细胞在炎症状态下发挥着核心作用，更好地了解它们的动力学可能为治疗提供机会。在本研究中，我们专注于鉴定和研究单核细胞在组织重塑过程中对棕色脂肪组织（BAT）功能的影响。对 BAT 免疫细胞的单细胞 RNA 测序分析揭示了单核细胞和巨噬细胞群体的巨大多样性。命运图谱实验表明，BAT 巨噬细胞池需要不断从单核细胞中得到补充。利用 BAT 扩张的遗传模型，我们发现这种情况下棕色脂肪单核细胞的数量会选择性增加。这一观察结果通过 CCR2 结合放射性示踪剂和正电子发射断层扫描得到了证实。重要的是，与它们的组织募集相一致，单核细胞计数减少，而骨髓造血不受影响。单核细胞耗竭可阻止棕色脂肪组织的扩张并改变其结构。足细胞蛋白聚糖的结合是 BAT 扩张的严格要求。总之，这些数据重新定义了 BAT 中免疫细胞的多样性，并强调了单核细胞募集在组织重塑中的作用。
