title: IL-17 expression by tubular epithelial cells in renal transplant recipients with acute antibody-mediated rejection.
abstract: 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.
authors.affiliation: Renal, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari.
authors.forename: A
authors.initials: A
authors.lastname: Loverre
authors.forename: T
authors.initials: T
authors.lastname: Tataranni
authors.forename: G
authors.initials: G
authors.lastname: Castellano
authors.forename: C
authors.initials: C
authors.lastname: Divella
authors.forename: M
authors.initials: M
authors.lastname: Battaglia
authors.forename: P
authors.initials: P
authors.lastname: Ditonno
authors.forename: M
authors.initials: M
authors.lastname: Corcelli
authors.forename: M
authors.initials: M
authors.lastname: Mangino
authors.forename: L
authors.initials: L
authors.lastname: Gesualdo
authors.forename: F P
authors.initials: FP
authors.lastname: Schena
authors.forename: G
authors.initials: G
authors.lastname: Grandaliano
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002461:Cell Line, Transformed; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism*; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D020381:Interleukin-17; D007518:Isoantibodies