Lymphoid neogenesis and immune infiltration in aged liver.

Abstract

Immune dysregulation and inflammation play a major role in the pathology of age-related disorders. In an earlier study, the microarray data from our laboratory indicated an increase in inflammation-related gene expression in the liver with age. We further investigated immune-related changes in the aged liver and found that the levels of inflammatory cytokines, chemokines, and inflammatory genes were higher in aged animals. Immunohistochemical studies showed that immune cells formed clusters or foci in the livers of old mice, preferentially near the perivascular regions. Further analysis revealed an enrichment of macrophages, T cells, B cells, natural killer cells, and neutrophils in old liver. Characterization of the immune clusters showed the presence of shared markers of tertiary lymphoid neogenesis. Levels of lymph node homing cytokines were elevated. Expression of immunoglobulin and recombinase gene transcripts was also higher, indicating the presence of ectopic lymphoid structures in the aged liver. Aged liver exhibits a marked inflammatory status accompanied by increased immune cell infiltration. Inflammation and ectopic lymphoid structures have previously been shown to be associated with carcinogenesis, a condition that becomes more prevalent with age. Thus, further study of inflammation-related changes in the microenvironment of the aged liver could provide insights into these disorders.