title: Differential effects of activated human renal epithelial cells on T-cell migration.
abstract: BACKGROUND
  Renal tubular epithelial cells (TECs) are one of the main targets of inflammatory insults during interstitial nephritis and kidney transplant rejection. While Th1 cells are know to be essential in the pathogenesis of rejection, the role of Th17 is still under debate. We hypothesize that TECs modulate the outcome of rejection process by production of distinct chemokines and cytokines that determine the attraction of different T-cell subsets. Therefore, we studied differential effects of activated human renal epithelial cells on T-cell migration.
  
  
  METHODS
  Human primary TECs were stimulated by IFN-γ and TNF-α in vitro. Chemokines and cytokines produced by activated TECs were measured using Luminex or ELISA. Chemotaxis assay was performed using activated peripheral blood mononuclear cells composed of CD4+CXCR3+ and CD4+CCR6+ T cells migrating towards stimulated and unstimulated TECs.
  
  
  RESULTS
  While activated TECs secreted abundant amounts of the pro-inflammatory cytokines IL-6 and IL-8, the T helper cell differentiation cytokines IL-1β, IL-12p70, IL-23 or TGF-β1 were not produced. The production of Th1 chemokines CXCL9, CXCL10 and CCL5 were significantly upregulated after TEC stimulation. In contrast, Th17 chemokine CCL20 could not be detected. Finally, activated TECs attracted significantly higher numbers of CD4+CXCR3+ T cells as compared to unstimulated TECs. No migration of CD4+CCR6+ T cells could be observed.
  
  
  CONCLUSIONS
  Activated primary renal tubular epithelial cells do not attract Th17 cells nor produce cytokines promoting Th17 cell differentiation in our experimental system mimicking the proinflammatory microenvironment of rejection.
authors.affiliation: Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands. m.demmers@erasmusmc.nl
authors.forename: Martijn W H J
authors.initials: MW
authors.lastname: Demmers
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Els
authors.initials: E
authors.lastname: van Beelen
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Ajda T
authors.initials: AT
authors.lastname: Rowshani
mesh_terms: D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines