Search

In murine peritoneal and other serous cavities, Gata6 drives identity of the major resident cavity macrophage population, with a smaller subset of cavity macrophages dependent upon Irf4. Here we show that Gata6+ macrophages in the human peritoneum are rare, regardless of age. Instead, many aligned with CD206+LYVE1+ mouse cavity macrophages from a differentiation stage just preceding expression of Gata6. The comparatively low abundance of CD206+ converting macrophages in healthy C57BL/6J mice was sustained after high-fat diet feeding or in mice capture from the wild, suggesting that the major resident macrophages between the species share overlapping differentiation programs but differing predispositions to distinct differentiation stages. Irf4-dependent mouse serous cavity macrophages aligned closely with CD1c+CD14+CD64+ human peritoneal dendritic cells (DCs) that, in turn, resembled CD1c+CD14-CD64- peritoneal cDC2. Peritoneal DC1 and plasmacytoid DCs were rare in both species. This cross-species resource comparing mouse and human serous cavity immune cells will facilitate translational research.

Brown adipose tissue (BAT) contains many immune cells. The presence of macrophages, monocytes, dendritic cells, T cells, B cells, and mast cells was documented in BAT. However, in comparison to white adipose tissue, relatively little is known on the impact of immune cells on BAT function. By directly interacting with BAT stromal cells, or by secreting pro- and anti-inflammatory mediators, immune cells modulate BAT activation and subsequently influence on adaptative thermogenesis and heat generation. In the current manuscript, we will focus on the diversity and functions of BAT immune cells.

Macrophages are found across all organs in the body and play key roles in health and disease. Systemic stress is a major risk factor for a variety of chronic inflammatory diseases. However, the primary source for stress hormones, the adrenal gland (AGs), have yet to be thoroughly assessed for immune cell diversity. Here we utilized single cell RNA-sequencing (scRNA-seq) to investigate macrophage heterogeneity in nascent AGs, compared against acute stress (cold challenge) or a chronic stress model of cardiovascular disease. In steady state, we observed two major macrophage populations in the AG. Following acute and chronic stress, AG macrophages upregulated expression of inflammatory cytokines (Il1b, TNFa) and key lipid uptake molecules, including Trem2. These observations were replicated using imaging analysis showing hormone uptake by AG macrophages. Using a monocyte-fate-mapping approach, we observed increased recruitment following stressed conditions, which correlated with reduced AG macrophage proliferation. Finally, we observed exacerbated systemic corticosterone levels following AG macrophage depletion and Trem2 deficiency. Overall, these data define AG macrophage heterogeneity and suggest a regulatory function of AG macrophage following exposure to acute and chronic stress.