Aging modulates homeostatic leukocyte trafficking to the peritoneal cavity in a sex-specific manner

Abstract

Aging is associated with exacerbated systemic inflammation (inflammaging) and the progressive loss of immune system function (immunosenescence). Leukocyte migration is necessary for effective immunity; however, dysregulated trafficking of leukocytes into tissue contributes to inflammaging and the development of age-related inflammatory diseases. Aging modulates leukocyte trafficking under inflammatory conditions; however, whether aging modulates leukocyte trafficking under homeostatic conditions remains to be elucidated. Although immune responses are evidently sexually dimorphic, limited studies have investigated the effect of sex on age-related changes to leukocyte trafficking processes. Here, we investigated age-related and sex-specific changes to the leukocyte populations within the peritoneal cavity of young (3-mo), middle-aged (18-mo) and old (21-mo) male and female wild-type mice in the steady state. We found an age-related increase in the number of leukocytes within the peritoneal cavity of female mice, predominantly B cells, which may reflect increased trafficking through this tissue with age. This was accompanied by an increased inflammatory environment within the aged cavity, including increased levels of chemoattractants, including B cell chemoattractants CXCL13 and CCL21, soluble adhesion molecules, and proinflammatory cytokines, which was more pronounced in aged female mice. Intravital microscopy techniques revealed altered vascular structure and increased vascular permeability within the peritoneal membrane of aged female mice, which may support increased leukocyte trafficking to the cavity with age. Together, these data indicate that aging affects homeostatic leukocyte trafficking processes in a sex-specific fashion.