T-CELL INTERLEUKIN-17 INDUCES STROMAL CELLS TO PRODUCE PROINFLAMMATORY AND HEMATOPOIETIC CYTOKINES

Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri. Here we report on the cloning o f human IL-17 (hIL-17), the human counterpart of murine IL-17. hIL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activ ated memory CD4(+) T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterp art, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony-stimul ating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34(+) hematopoietic progenitors and their preferential maturatio n into neutrophils. These observations suggest that hIL-17 may constit ute (a) an early initiator of the T cell-dependent inflammatory reacti on; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.