B-cell Interleukin 1 Receptor 1 modulates the female adipose tissue immune microenvironment during aging

The Nod like receptor protein 3 (NLRP3) inflammasome and its product interleukin-1ß (IL-1ß) drive inflammaging in visceral adipose tissue (vWAT) and contribute to the expansion of interleukin-1 receptor 1 (Il1r1) positive aged adipose B-cells (AABs). AABs promote metabolic dysfunction and inflammation under inflammatory challenges. However, it is unclear whether IL-1ß contributes to AAB-associated inflammation during aging. Using a B-cell specific knockout of Il1r1 (BKO mice), we characterized old vWAT in the absence of IL-1ß – B-cell signaling. In addition to sex-specific metabolic improvements in females, we identified a reduction in the proportion of B-cells and a sex-specific increase in the B1:B2 B-cell ratio in BKO vWAT. Using single cell RNA-sequencing of vWAT immune cells, we observed that BKO differentially affected inflammatory signaling in vWAT immune cells. These data suggest that IL-1ß – B-cell signaling supports the inflammatory response in multiple cell types and provides insight into the complex microenvironment in aged vWAT. Overall design: Single cell RNA sequencing (10x genomics) on sorted CD45+ live cells from the visceral adipose tissue of 3m WT (n=2), 22m WT (n=3), and 22m IL1R1 fl/fl CD19cre+ (n=3) female mice challenged with 0.1 mg/kg LPS for 4 hours.