Interleukin-13 is Expressed in Mouse Kidney Allograft Rejection and Mediates Proliferation of Renal Tubular Epithelium In Vitro

Kidney transplantation is the preferred therapy for kidney failure. The leading cause of graft loss is chronic allograft nephropathy (CAN). We hypothesize that Interleukin-13 (IL-13), protective against acute kidney graft rejection, is involved in CAN. In mouse kidney allografts, we observe after 2 weeks signs of interstitial inflammation progressing to vasculitis. By 6 weeks, CAN is manifest. IL-13 is overexpressed in allografts versus isografts (p<0.01) throughout the post-transplant course. Concomitantly, we detect markers of fibrogenesis and epithelial-mesenchymal transition. To explore this phenomenon, kidney proximal tubular epithelial cells were cultured with IL-13. Within 6 hours, we show increased proliferation compared to untreated cells (p<0.01), occurring through activation of IL4R /JAK3 and Stat6 and blocked by anti-IL-13 monoclonal antibody. This is the first report of IL-13 inducing a specific biological activity in kidney epithelial cells with a possible role in the damage control machinery, indicating its potential as a biomarker and thera-