Oxidized LDL modulates apoptosis of regulatory T cells in patients with ESRD.

Détails

ID Serval
serval:BIB_70AF63850752
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Oxidized LDL modulates apoptosis of regulatory T cells in patients with ESRD.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Meier P., Golshayan D., Blanc E., Pascual M., Burnier M.
ISSN
1533-3450[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
20
Numéro
6
Pages
1368-1384
Langue
anglais
Résumé
Increased levels of oxidized low-density lipoproteins (oxLDL) contribute to the increased risk for atherosclerosis, which persists even after adjusting for traditional risk factors, among patients with ESRD. Regulatory T cells (CD4+/CD25+ Tregs), which down-regulate T cell responses to foreign and self-antigens, are protective in murine atherogenesis, but whether similar immunoregulation occurs in humans with ESRD is unknown. Because cellular defense systems against oxLDL involve proteolytic degradation, the authors investigated the role of oxLDL on proteasome activity of CD4+/CD25+ Tregs in patients with ESRD. CD4+/CD25+ Tregs isolated from uremic patients' peripheral blood, especially that of chronically hemodialyzed patients, failed to suppress cell proliferation, exhibited cell-cycle arrest, and entered apoptosis by altering proteasome activity. Treating CD4+/CD25+ Tregs with oxLDL or uremic serum ex vivo decreased the number and suppressive capacity of CD4+/CD25+ Tregs. In vitro, oxLDL promoted the accumulation of p27Kip1, the cyclin-dependent kinase inhibitor responsible for G1 cell cycle arrest, and increased apoptosis in a time- and concentration-dependent manner. In summary, proteasome inhibition by oxLDL leads to cell cycle arrest and apoptosis, dramatically affecting the number and suppressive capacity of CD4+/CD25+ Tregs in chronically hemodialyzed patients. This response may contribute to the immune dysfunction, microinflammation, and atherogenesis observed in patients with ESRD.
Mots-clé
Adult, Antigens, CD95/metabolism, Apoptosis, Case-Control Studies, Cells, Cultured, Coculture Techniques, Cyclin-Dependent Kinase Inhibitor p27/metabolism, Female, Forkhead Transcription Factors/metabolism, G1 Phase, Humans, Interleukin-2 Receptor alpha Subunit/metabolism, Kidney Failure, Chronic/immunology, Lipoproteins, LDL/physiology, Male, Middle Aged, Phenotype, Phytohemagglutinins, Proteasome Endopeptidase Complex/metabolism, T-Lymphocytes, Regulatory/physiology, Uremia/immunology, bcl-2-Associated X Protein/metabolism, bcl-X Protein/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/09/2009 9:04
Dernière modification de la notice
20/08/2019 14:29
Données d'usage