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, & Wilkinson, Ray (2015) The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function. PLoS ONE, 10(7), e0134688.
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.
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|Item Type:||Journal Article|
|Additional Information:||Unmapped bibliographic data:
C7 - e0134688 [EPrints field already has value set]
DB - Scopus [Field not mapped to EPrints]
AD - Conjoint Kidney Research Laboratory, Pathology Queensland, Brisbane, QLD, Australia [Field not mapped to EPrints]
AD - Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia [Field not mapped to EPrints]
AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia [Field not mapped to EPrints]
AD - Medical School, University of Queensland, Brisbane, QLD, Australia [Field not mapped to EPrints]
|Divisions:||Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
|Copyright Owner:||Copyright 2015 Sampangi et al|
|Copyright Statement:||This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Deposited On:||08 Jan 2016 02:53|
|Last Modified:||10 Jan 2016 21:58|
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