Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

被引:0
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作者
Anis Larbi
Carl Fortin
Gilles Dupuis
Hicham Berrougui
Abdelouahed Khalil
Tamas Fulop
机构
[1] Agency for Science,Singapore Immunology Network (SIgN), Biopolis
[2] Technology and Research (A*STAR),Research Center on Aging
[3] University of Sherbrooke,Clinical Research Center, Faculty of Medicine
[4] University of Sherbrooke,undefined
来源
AGE | 2014年 / 36卷
关键词
Aging; Immunosenescence; HDL; Inflamm-Aging; Metabolic pathways;
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摘要
Natural aging is accompanied by a dysregulation of the host immune response that has well-known clinical consequences but poorly defined underlying causes. It has previously been reported that advancing age is associated with an increase in membrane cholesterol level in T cells. The aim of this study was to investigate whether high-density lipoprotein (HDL) can modulate the age-related accumulation of membrane cholesterol in T cells and impact on their subsequent responsiveness. Our data reveal that cholesterol metabolism, influx, and efflux are altered in T cells with aging, which may in part explain the increase in membrane cholesterol level observed in T cells in elderly individuals. HDL was unable to promote reverse cholesterol transport in T cells from elderly subjects with the same efficiency as was observed in T cells from young subjects besides unchanged ABCA-1 and SR-BI expressions. HDL exhibited a short-acting co-stimulatory effect by enhancing T cell production of interleukin-2 (IL-2). Moreover, HDL from healthy normolipemic individuals exerted differential effects on T cell proliferation that depended on the age of the HDL donor. Finally, HDL modulated TCR/CD28 activation by inducing sustained signaling through pLck, pERK, and pAkt. These data suggest that HDL has immunomodulatory effects on T cells that are influenced by age.
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