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, G. Grandaliano

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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. 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.

Original languageEnglish
Pages (from-to)1248-1259
Number of pages12
JournalAmerican Journal of Transplantation
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2011

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Keywords

  • Complement system
  • epithelial tubular cells
  • IL-17
  • kidney transplantation
  • renal acute rejection

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Loverre, A., Tataranni, T., Castellano, G., Divella, C., Battaglia, M., Ditonno, P., Corcelli, M., Mangino, M., Gesualdo, L., Schena, F. P., & Grandaliano, G. (2011). IL-17 expression by tubular epithelial cells in renal transplant recipients with acute antibody-mediated rejection. American Journal of Transplantation, 11(6), 1248-1259. https://doi.org/10.1111/j.1600-6143.2011.03529.x