T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines

doi:10.1084/jem.183.6.2593

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T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines

F Fossiez, O Djossou, P Chomarat, L Flores-Romo, S Ait-Yahia, C Maat, JJ Pin, P Garrone, E Garcia, S Saeland, D Blanchard, C Gaillard, B Das Mahapatra, E Rouvier, P Golstein, J Banchereau and S Lebecque
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.

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 of 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 activated memory CD4+ T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterpart, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony- stimulating 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 maturation into neutrophils. These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.
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