An Indispensable Role for STAT1 in IL-27-Induced T-bet Expression but Not Proliferation of Naive CD4+ T Cells

• Published in: The Journal of immunology (1950) 2004-09, Vol.173 (6), p.3871-3877
• Main Authors: Kamiya, Sadahiro, Owaki, Toshiyuki, Morishima, Noriko, Fukai, Fumio, Mizuguchi, Junichiro, Yoshimoto, Takayuki
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - physiology; Animals; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - enzymology; CD4-Positive T-Lymphocytes - immunology; Cell Division - genetics; Cell Division - immunology; Cell Line; Cells, Cultured; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Enzyme Activation - immunology; Histocompatibility Antigens Class I - biosynthesis; Humans; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interleukin-12 - physiology; Interleukins - physiology; Interphase - genetics; Interphase - immunology; Janus Kinase 1; Janus Kinase 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Milk Proteins - metabolism; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Receptors, Interleukin - antagonists & inhibitors; Receptors, Interleukin - biosynthesis; Receptors, Interleukin-12; Signal Transduction - genetics; Signal Transduction - immunology; STAT1 Transcription Factor; STAT2 Transcription Factor; STAT3 Transcription Factor; STAT5 Transcription Factor; T-Box Domain Proteins; Trans-Activators - deficiency; Trans-Activators - genetics; Trans-Activators - metabolism; Trans-Activators - physiology; Transcription Factors - antagonists & inhibitors; Transcription Factors - biosynthesis; TYK2 Kinase
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.6.3871

IL-27 is a novel IL-12 family member that plays a role in the early regulation of Th1 initiation, induces proliferation of naive CD4+ T cells, and synergizes with IL-12 in IFN-gamma production. It has been recently reported that IL-27 induces T-bet and IL-12Rbeta2 expression through JAK1/STAT1 activation. In the present study, we further investigated the JAK/STAT signaling molecules activated by IL-27 and also the role of STAT1 in IL-27-mediated responses using STAT1-deficient mice. In addition to JAK1 and STAT1, IL-27-activated JAK2, tyrosine kinase-2, and STAT2, -3, and -5 in naive CD4+ T cells. The activation of STAT2 and STAT5, but not of STAT3, was greatly diminished in STAT1-deficient naive CD4+ T cells. Comparable proliferative response to IL-27 was observed between STAT1-deficient and wild-type naive CD4+ T cells. In contrast, IL-27 hardly induced T-bet and subsequent IL-12Rbeta2 expression, and synergistic IFN-gamma production by IL-27 and IL-12 was impaired in STAT1-deficient naive CD4+ T cells. Moreover, IL-27 augmented the expression of MHC class I on naive CD4+ T cells in a STAT1-dependent manner. These results suggest that IL-27 activates JAK1 and -2, tyrosine kinase-2, STAT1, -2, -3, and -5 in naive CD4+ T cells and that STAT1 plays an indispensable role in IL-27-induced T-bet and subsequent IL-12Rbeta2 expression and MHC class I expression as well but not proliferation, while STAT3 presumably plays an important role in IL-27-induced proliferation.