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.
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.
Authors: Becker M P Law; Ray Wilkinson; Xiangju Wang; Katrina Kildey; Kurt Giuliani; Kenneth W Beagley; Jacobus Ungerer; Helen Healy; Andrew J Kassianos Journal: J Am Soc Nephrol Date: 2019-06-11 Impact factor: 10.121
Authors: Maritza J Romero; Lin Yao; Supriya Sridhar; Anil Bhatta; Huijuan Dou; Ganesan Ramesh; Michael W Brands; David M Pollock; Ruth B Caldwell; Stephen D Cederbaum; C Alvin Head; Zsolt Bagi; Rudolf Lucas; Robert W Caldwell Journal: Front Immunol Date: 2013-12-24 Impact factor: 7.561
Authors: Xiangju Wang; Ray Wilkinson; Katrina Kildey; Jeremy Potriquet; Jason Mulvenna; Richard J Lobb; Andreas Möller; Nicole Cloonan; Pamela Mukhopadhyay; Andrew J Kassianos; Helen Healy Journal: J Extracell Vesicles Date: 2017-04-21
Authors: Ray Wilkinson; Xiangju Wang; Andrew J Kassianos; Steven Zuryn; Kathrein E Roper; Andrew Osborne; Sandeep Sampangi; Leo Francis; Vishwas Raghunath; Helen Healy Journal: PLoS One Date: 2014-01-27 Impact factor: 3.240
Authors: Muhammad Ali Khan; Xiangju Wang; Kurt T K Giuliani; Purba Nag; Anca Grivei; Jacobus Ungerer; Wendy Hoy; Helen Healy; Glenda Gobe; Andrew J Kassianos Journal: Int J Mol Sci Date: 2020-01-15 Impact factor: 5.923