The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function

Sampangi, Sandeep, Kassianos, Andrew J., Wang, Xiangju, Beagley, Kenneth W., Klein, Travis, Afrin, Sadia, Healy, Helen and Wilkinson, Ray (2015) The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function. PLoS One, 10 7: . doi:10.1371/journal.pone.0134688

Author Sampangi, Sandeep
Kassianos, Andrew J.
Wang, Xiangju
Beagley, Kenneth W.
Klein, Travis
Afrin, Sadia
Healy, Helen
Wilkinson, Ray
Title The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-07
Sub-type Article (original research)
DOI 10.1371/journal.pone.0134688
Open Access Status DOI
Volume 10
Issue 7
Total pages 13
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2016
Language eng
Abstract Proximal tubule epithelial cells (PTEC) of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC) as the model system. We demonstrate that PTEC express three inhibitory molecules: (i) cell surface PD-L1 that induces MoDC expression of PD-L1; (ii) intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii) soluble HLA-G (sHLA-G) that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.
Keyword Tubular cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
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