Tax protein of human T-cell leukaemia virus type 1 induces interleukin 17 gene expression in T cells

1 Virologie Humaine INSERM-U412, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences Lyon-Gerland, 46 allée d'Italie, 69364 Lyon Cedex 07, France 2 Biologie Moléculaire de la Différenciation, Université Paris 7 Denis Diderot, 2 place Jussieu, case 7136, 75251 Paris Cedex 05, France Correspondence Madeleine Duc Dodon madeleine.duc.dodon{at}ens-lyon.fr Tax protein of human T-cell leukaemia virus type 1 (HTLV-1) induces the expression of several cellular genes that are involved in T cell activation and proliferation. In this study, it was observed that Tax upregulated the expression of human interleukin 17 (IL17), a cytokine mainly produced by activated CD4 + memory T cells. Indeed, IL17 mRNA was highly expressed in HTLV-1-infected T cells as well as in Tax-expressing Jurkat T cells, whereas it was not detectable in HTLV-1-negative T cell lines. The clinical relevance of these observations was further demonstrated by quantitative assessment of IL17 expression in lymphocytes isolated from one HTLV-1-infected patient. To define the transcriptional activation of the IL17 gene by Tax, the 5'-flanking region of this gene was cloned and a reporter gene analysis performed. The presence of a Tax-responsive region spanning 614 bp upstream of the initiation start site was identified, in HeLa as well as in Jurkat cells, stimulated with phorbol myristate acetate and Ca 2+ ionophore. Finally, Tax mutants were used to show that the transcriptional activation of the IL17 promoter by Tax was dependent on the CREB/ATF pathway. As IL17 upregulates the expression of several pro-inflammatory cytokines, these observations provide new insights into the involvement of the Tax protein in the pathophysiology of HTLV-1-associated inflammatory disorders. Present address: Department of Biochemistry, University of Cambridge, UK.