B-cell Interleukin 1 Receptor 1 (IL1R1) modulates the female adipose tissue immune microenvironment during aging.

Abstract

Myeloid cell production of interleukin-1β (IL-1β) drives inflammaging in visceral adipose tissue (vWAT) and contributes 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-1β 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-1β - 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-1β - B-cell signaling supports the inflammatory response in multiple cell types and provides insight into the complex microenvironment in aged vWAT.