IL-17 expression by tubular epithelial cells in renal transplant recipients with acute antibody-mediated rejection

A. Loverre, T. Tataranni, G. Castellano, C. Divella, M. Battaglia, P. Ditonno, M. Corcelli, M. Mangino, L. Gesualdo, F. P. Schena, Giuseppe Grandaliano

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Acute rejection is still a common complication of kidney transplantation. IL-17 is known to be associated with allograft rejection but the cellular source and the role of this cytokine remains unclear. We investigated IL-17 graft expression in renal transplant recipients with acute antibody-mediated rejection (ABMR), acute T-cell-mediated rejection (TCMR), interstitial fibrosis and tubular atrophy (IFTA) and acute tubular damage due to calcineurin-inhibitor toxicity (CNI). In acute ABMR, tubular IL-17 protein expression was significantly increased compared to TCMR, where most of the IL-17 +cells were CD4+graft infiltrating lymphocytes, IFTA and CNI control groups. The tubular expression of IL-17 in acute ABMR colocalized with JAK2 phosphorylation and peritubular capillaries C4d deposition. In addition, IL-17 tubular expression was directly and significantly correlated with the extension of C4d deposits. In cultured proximal tubular cells, C3a induced IL-17 gene and protein expression along with an increased in JAK2 phosphorylation. The inhibition of JAK2 abolished C3a-induced IL-17 expression. The use of steroids and monoclonal antibodies reduced IL-17 expression, JAK2 phosphorylation and C4d deposition in acute ABMR patients. Our data suggest that tubular cells represent a significant source of IL-17 in ABMR and this event might be mediated by the complement system activation featuring this condition. The authors demonstrate that tubular epithelial cells represent a significant source for IL-17 in acute antibody-mediated rejection through the activation of the complement cascade and JAK2 phosphorylation that, in the clinical area, may represent a suitable therapeutic target. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
Original languageEnglish
Pages (from-to)1248-1259
Number of pages12
JournalAmerican Journal of Transplantation
Publication statusPublished - 2011


  • Base Sequence
  • Blotting, Western
  • Cell Line, Transformed
  • Complement system
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Graft Rejection
  • Humans
  • IL-17
  • Immunohistochemistry
  • Interleukin-17
  • Isoantibodies
  • Kidney Transplantation
  • Kidney Tubules
  • Microscopy, Confocal
  • Polymerase Chain Reaction
  • epithelial tubular cells
  • kidney transplantation
  • renal acute rejection


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