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.

Loverre, A., Tataranni, T., Castellano, G., Divella, C., Battaglia, M., Ditonno, P., Corcelli, M., Mangino, M., Gesualdo, L., Schena, F. P., Grandaliano, G., IL-17 expression by tubular epithelial cells in renal transplant recipients with acute antibody-mediated rejection, <<AMERICAN JOURNAL OF TRANSPLANTATION>>, 2011; 11 (6): 1248-1259. [doi:10.1111/j.1600-6143.2011.03529.x] [http://hdl.handle.net/10807/196983]

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

F. P.; Grandaliano
2011

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. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
Inglese
Loverre, A., Tataranni, T., Castellano, G., Divella, C., Battaglia, M., Ditonno, P., Corcelli, M., Mangino, M., Gesualdo, L., Schena, F. P., Grandaliano, G., IL-17 expression by tubular epithelial cells in renal transplant recipients with acute antibody-mediated rejection, <<AMERICAN JOURNAL OF TRANSPLANTATION>>, 2011; 11 (6): 1248-1259. [doi:10.1111/j.1600-6143.2011.03529.x] [http://hdl.handle.net/10807/196983]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/196983
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