NLRP3 inflammasome controls adipose tissue leukocytosis and inflammation during aging (INM6P.331)

Abstract Aging is associated with chronic inflammation and increased risk for degenerative disorders and diseases. In the elderly there is increased visceral adiposity and increased numbers of fat-associated lymphocyte clusters within adipose tissue (AT); however the role for AT in age-induced immune defects is unclear. Our prior studies have identified that the canonical inflammasome, NLRP3, is required for diet-induced AT inflammation and age-related inflammation in multiple organs. We hypothesized that NLRP3 is required for age-induced changes in AT immune cells and metabolic dysfunction. We found that aging increases AT lymphocytes; compared to 24month old control mice, Nlrp3-/- animals were protected from increases in AT leukocytosis. RNA sequencing analysis of AT macrophages and B cells from aged mice revealed distinct inflammatory signatures that were regulated by NLRP3. AT displayed immunological properties, as during infection, a higher frequency of antigen specific T cells are recruited to AT than to spleen. Our results show that NLRP3 is required for age-induced T follicular cell and B cell infiltration into visceral AT. Furthermore, our data suggests that pharmacological inhibition of NLRP3 activation and IL-1β signaling may improve AT inflammation and insulin resistance in aged mice. These data demonstrates that macrophage-expressed NLRP3 inflammasome controls age-related inflammation and AT microenvironment by secondary effects on T and B cell subpopulations.