Distinct Roles of Transforming Growth Factor-beta-activated Kinase 1 (TAK1)-c-Rel and Interferon Regulatory Factor 4 (IRF4) Pathways in Human T Cell Lymphotropic Virus 1-transformed T helper 17 Cells Producing Interleukin-9

作者：Refaat Alaa; Zhou Yue; Suzuki Shunsuke; Takasaki Ichiro; Koizumi Keiichi; Yamaoka Shoji; Tabuchi Yoshiaki; Saiki Ikuo; Sakurai Hiroaki^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286(24): 21092-21099.

DOI：10.1074/jbc.M110.200907

Investigation of helper T cell markers in HTLV-1-transformed cell lines demonstrated that HuT-102 has an IL-9-producing Th17 phenotype. We confirmed the vital role of retinoic acid-related orphan receptor C, a Th17 transcription factor, in the expression of IL-17. Interferon regulatory factor 4 (IRF4), a transcription factor overexpressed in all HTLV-1-infected cells, regulated IL-17 and IL-9 concomitantly. We further demonstrated a novel pathway for the regulation of Tax-induced cytokines, IL-9 and IL-6, through TAK1-mediated nuclear accumulation of c-Rel. A microarray analysis for IRF4 knocked down HuT-102 cells showed a significant up-regulation in the set of genes related to Th1, mainly IFN-gamma and several transcription factors. T-bet and IRF1, but not STAT1 and IRF9, participated in counteracting the inhibitory effect of IRF4 on the production of IFN-gamma. Finally, suppression of both IRF4 and c-Rel resulted in the reduced proliferation. Collectively, these findings indicate that TAK1-c-Rel and IRF4 pathways play distinct roles in the maintenance of IL-9-producing Th17 phenotype of HTLV-1-transformed cells.

• 出版日期2011-6-17