C-reactive protein promotes acquisition of a senescent phenotype in human CD8+ T cells
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1
University of California, Los Angeles, Pathology and Laboratory Medicine, United States
C-reactive protein (CRP), a robust biomarker of systemic inflammation, is the prototypic atherosclerosis risk predictor. Chronically high CRP serum levels are also strongly associated with elevated risk of type 1 diabetes, cancer, osteoporosis, as well as poor health, frailty, and increased all-cause mortality in older persons. In HIV/AIDS, high CRP levels correlate with accelerated disease progression, independent of CD4+ T cell counts and HIV RNA levels. Thus, CRP, rather than being simply an inflammatory biomarker, may play a causal role in modulating the immune system.
In the present study, we evaluated the effects of “high-risk,” physiologic concentrations of human CRP on the molecular/genetic signature and senescence trajectory of human CD8+ T cells. Following binding to surface LOX-1 and Fc receptors on CD8+ T cells, CRP treatment led to down-regulation of CD28 surface expression, significantly reduced telomerase activity and hTERT gene expression, accelerated telomere loss, and reduced IL-2 transcription. In addition, CRP exposure increased TNF-α production and COX-2 activity, suggesting that in persons with elevated CRP levels, CD8+ T cells may be contributing to the observed systemic inflammation. CRP was also found to increase T cell secretion of RANKL, a key mediator of bone breakdown. To our knowledge, this is the first study to document the potential effects and pathways by which CRP accelerates cellular aging of human T cells. Our data suggest that blocking interactions between CRP and its receptors may provide novel strategies for targeted therapy for multiple human pathologies associated with chronic inflammation. (Supported by NIH AG032422).
Keywords:
Replicative Senescence,
CD8+ T cells,
Telomerase,
C-Reactive Protein,
RANKL
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Chou
JP,
Ryba
DM,
Koduri
MP and
Effros
RB
(2013). C-reactive protein promotes acquisition of a senescent phenotype in human CD8+ T cells.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00233
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Received:
11 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Jennifer P Chou, University of California, Los Angeles, Pathology and Laboratory Medicine, Los Angeles, CA, 90095, United States, jenpchou@ucla.edu