Human proximal tubule epithelial cells modulate autologous dendritic cell function

Kassianos, Andrew J., Sampangi, Sandeep, Wang, Xiangju, Roper, Kathrein E., Beagley, Ken, Healy, Helen and Wilkinson, Ray (2013) Human proximal tubule epithelial cells modulate autologous dendritic cell function. Nephrology Dialysis Transplantation, 28 2: 303-312. doi:10.1093/ndt/gfs136

Author Kassianos, Andrew J.
Sampangi, Sandeep
Wang, Xiangju
Roper, Kathrein E.
Beagley, Ken
Healy, Helen
Wilkinson, Ray
Title Human proximal tubule epithelial cells modulate autologous dendritic cell function
Journal name Nephrology Dialysis Transplantation   Check publisher's open access policy
ISSN 0931-0509
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.1093/ndt/gfs136
Volume 28
Issue 2
Start page 303
End page 312
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2014
Language eng
Formatted abstract
Background: We have previously demonstrated that human kidney proximal tubule epithelial cells (PTEC) are able to modulate autologous T and B lymphocyte responses. It is well established that dendritic cells (DC) are responsible for the initiation and direction of adaptive immune responses and that these cells occur in the renal interstitium in close apposition to PTEC under inflammatory disease settings. However, there is no information regarding the interaction of PTEC with DC in an autologous human context.

Methods: Human monocytes were differentiated into monocyte-derived DC (MoDC) in the absence or presence of primary autologous activated PTEC and matured with polyinosinic:polycytidylic acid [poly(I:C)], while purified, pre-formed myeloid blood DC (CD1c+ BDC) were cultured with autologous activated PTEC in the absence or presence of poly(I:C) stimulation. DC responses were monitored by surface antigen expression, cytokine secretion, antigen uptake capacity and allogeneic T-cell-stimulatory ability.

Results: The presence of autologous activated PTEC inhibited the differentiation of monocytes to MoDC. Furthermore, MoDC differentiated in the presence of PTEC displayed an immature surface phenotype, efficient phagocytic capacity and, upon poly(I:C) stimulation, secreted low levels of pro-inflammatory cytokine interleukin (IL)-12p70, high levels of anti-inflammatory cytokine IL-10 and induced weak Th1 responses. Similarly, pre-formed CD1c+ BDC matured in the presence of PTEC exhibited an immature tolerogenic surface phenotype, strong endocytic and phagocytic ability and stimulated significantly attenuated T-cell proliferative responses.

Conclusions: Our data suggest that activated PTEC regulate human autologous immunity via complex interactions with DC. The ability of PTEC to modulate autologous DC function has important implications for the dampening of pro-inflammatory immune responses within the tubulointerstitium in renal injuries. Further dissection of the mechanisms of PTEC modulation of autologous immune responses may offer targets for therapeutic intervention in renal medicine.

Keyword Dendritic cells
Immune modulation
Proximal tubule epithelial cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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