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FcIL-17, a T cell-derived cytokine, stimulates stromal cells from various tissues to secrete IL-6, IL-8, G-CSF and PGE_, not only suggesting a proinflammatory role for IL-17, but also supporting an indirect hematopoietic activity. In addition to inducing cytokine production, IL-17 enhances the ability of fibroblasts to sustain growth of CD34+ hematopoietic progenitors, and directs their maturation into neutrophils (Fossiez et al, J. Exp. Med. 1996; 183:2593). We hypothesized that IL-17 might support the maturation of DC from CD34+ bone marrow progenitors and/or influence the allostimulatory capacity of these cells. Purpose: Our aim was to examine the influence of IL-17 on DC maturation, and to ascertain the role of IL-17 in alloimmune responses both in vivo and in vitro. Methods: To examine the possible effects of IL-17 on DC maturation. GM-CSF-stimulated BM-derived immature DC were treated with recombinant mouse (rm) IL-17. Following treatment, the cells were analyzed by flow cytometry for the expression of various surface markers. They were also tested as stimulators in a 3-day primary mixed leukocyte reaction (MLR). We also determined the influence of a soluble rmIL-17R: Fc fusion protein (Yao et al, Immunity 1995, 3:811) on alloimmune responses both in vitro and in vivo. The in vivo immunosuppressive efficacy of rmlL-17R.Fc was tested in a vascularized model of cardiac allograft rejection, using the B10 to C3H strain combination. The fusion protein or control Ig was administered i.p. at various doses (100-500 _g/day) and for different durations post transplant. Results: IL-17 promoted the maturation of DC as evidenced by increased expression of co-stimulatory molecules (CD40. CD8O. CD86). CD11c and MHC class II on the cell surface. IL-17 also augmented the allostimulatory capacity of these cells, as evidenced by an increase in T cell reactivity. The influence of rm IL- 17R:Fc fusion protein on a primary MLR was compared with that of a control molecule, human IgGI Compared with IgG-treated control MLR cultures, rmIL-17R:Fc markedly inhibited alloantigen-induced lymphocyte proliferation at concentrations of 50.200pg/ml Median survival time of vascularized grafts was prolonged significantly from 10.5 days to 19 days in mice treated with rm IL-17R.Fc at a dose of 5OOpg/day from days O-6 Conclusions: The results suggest a role for IL-17 in DC maturation with consequent effects on T cell stimulation. The novel finding that rmIL~17R Fc can enhance organ graft survival further indicates a role for IL-17 in alloimmunity, and that his molecule may provide a target for therapeutic intervention.