Abstract 167: Immunomodulatory Properties of HDL are Associated with Lipidomic and Proteomic Composition and are Modifiable by Diet

Abstract

HDL is proposed to be an important immune regulator; however, the direct effects of HDL lipidomic and proteomic composition on immune activity, and the capacity to modulate immunomodulatory properties of HDL through dietary intervention, requires further study. We hypothesized that daily intake of different egg-based diets, which we have reported to induce HDL lipidome and proteome remodeling, would correspond to changes in the capacity of HDL to modulate macrophage and T cell inflammation. Healthy men and women (n = 26) participated in a 16-week randomized, crossover intervention trial in which they followed a 4-week egg-free diet, followed by random assignment to a 4-week diet period in which they consumed 3 whole eggs/day or 3 egg whites/day. Subjects then switched to the alternative egg treatment following a second 4-week egg-free washout period. Fasted blood samples were collected after each diet period to isolate HDL for compositional analysis and perform immune activation assays. We observed that subject-derived HDL increased lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) secretion from RAW 264.7 macrophages following the whole egg diet period, whereas there was a trend toward reduced LPS-induced interleukin 6 (IL-6) secretion and no effect on IL-10. Further, HDL dose-dependently increased Jurkat T cell counts and interleukin-2 (IL-2) secretion following activation, and these changes were inversely associated with lipid raft formation. HDL following the whole egg period increased IL-2 secretion from activated T cells, with greater increases in cell numbers observed in female subjects. Interestingly, changes in HDL-phosphatidylcholine, -phosphatidylethanolamine, and -ceramide species correlated with changes in macrophage TNFα between diet periods, whereas changes in macrophage IL-1β and T cell IL-2 were associated with changes in HDL-triacylglycerol and sphingomyelin species. Changes in macrophage and T cell cytokine production correlated with changes in 25 and 34 HDL proteins, respectively, but not HDL-cholesterol or cholesterol efflux capacity. HDL lipidomic and proteomic composition are determinants of its immunomodulatory properties, which can be modified through dietary intervention.