Differentiation of monocyte derived dendritic cells in end stage renal disease is skewed towards accelerated maturation

Abstract

Background: Dendritic cells (DC) play an important role in the induction of immune responses. Patients with end stage renal disease (ESRD) suffer from chronic inflammation, leading to a secondary, uremic immunodeficiency associated with alterations in monocyte subpopulations with increased proinflammatory capacities. Objectives: The aim of this study was to examine, under isolated conditions, whether alterations in monocyte subpopulations may affect in vitro maturation of dendritic cells (DC) in patients with ESRD, thus allowing us to draw conclusions for the situation in vivo. Material and Methods: Monocytes from 30 patients undergoing hemodialysis (HD) and 15 healthy volunteers were enriched from peripheral blood leukocytes, differentiated into immature DC (iDC) in medium containing IL-4 and GM-CSF, and were induced with LPS to differentiate into mature DC (mDC). Monocyte subpopulations and DC maturation stages were phenotypically characterized using flow-cytometry. Results: Although phenotypically indistinguishable, the number of both iDC and mDC that were generated from uremic monocytes was significantly higher compared to those from healthy controls (p = 0.02 and p = 0.03, respectively). This was associated with an increased number of CD14+ CD16+ monocytes (p = 0.02) and by a higher maturation efficiency of mDC in patients (p = 0.04). Conclusions: A high percentage of CD14+ CD16+ monocytes in patients with ESRD is associated with an increased propensity to differentiate into DC. This indicates that chronic inflammation may substantiate the biased consistence of monocyte subpopulations leading to profound alteration in DC generation and maturation in ESRD.