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Article Dans Une Revue Journal of Immunology Année : 2009

Oxidative Stress Mediates a Reduced Expression of the Activating Receptor NKG2D in NK Cells from End-Stage Renal Disease Patients

Marie-Noëlle Peraldi
  • Fonction : Auteur
Jeannig Berrou
  • Fonction : Auteur
Nicolas Dulphy
  • Fonction : Auteur
Alexandre Seidowsky
  • Fonction : Auteur
Philippe Haas
  • Fonction : Auteur
Nicolas Boissel
  • Fonction : Auteur
Fabien Metivier
  • Fonction : Auteur
Christine Randoux
  • Fonction : Auteur
Niloufar Kossari
  • Fonction : Auteur
Alain Guérin
  • Fonction : Auteur
Sylvie Geffroy
  • Fonction : Auteur
Guy Delavaud
  • Fonction : Auteur
Denis Glotz
  • Fonction : Auteur
Dominique Charron
  • Fonction : Auteur
Antoine Toubert
  • Fonction : Auteur

Résumé

Abstract To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D+ cells within both the CD8+ T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56dim cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56bright cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both increased membrane-bound MHC class I-related chain A (MICA) on monocytes (p = 0.04) and increased soluble MICA (203 pg/ml vs 110 pg/ml; p < 0.001). Both ROS and uremic serum could significantly increase in vitro the expression of the NKG2D ligand MICA on the renal epithelial cell line HK-2. Taken together, these studies suggest for the first time that both low NKG2D expression and up-regulation of its ligand MICA are related to ROS production and may be involved in the immune deficiency of ESRD patients.

Dates et versions

hal-04514874 , version 1 (26-03-2024)

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Marie-Noëlle Peraldi, Jeannig Berrou, Nicolas Dulphy, Alexandre Seidowsky, Philippe Haas, et al.. Oxidative Stress Mediates a Reduced Expression of the Activating Receptor NKG2D in NK Cells from End-Stage Renal Disease Patients. Journal of Immunology, 2009, 182 (3), pp.1696 - 1705. ⟨10.4049/jimmunol.182.3.1696⟩. ⟨hal-04514874⟩

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