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

作者: Sadahiro Kamiya , Toshiyuki Owaki , Noriko Morishima , Fumio Fukai , Junichiro Mizuguchi

DOI: 10.4049/JIMMUNOL.173.6.3871

关键词: ZAP70STAT5BiologyInterleukin 27CD28Cell biologySTAT4MHC class IInterleukin 21Cytotoxic T cell

摘要: IL-27 is a novel IL-12 family member that plays role in the early regulation of Th1 initiation, induces proliferation naive CD4 + T cells, and synergizes with IFN-γ production. It has been recently reported T-bet IL-12Rβ2 expression through JAK1/STAT1 activation. In present study, we further investigated JAK/STAT signaling molecules activated by also STAT1 IL-27-mediated responses using STAT1-deficient mice. addition to JAK1 STAT1, IL-27-activated JAK2, tyrosine kinase-2, STAT2, -3, -5 cells. The activation STAT2 STAT5, but not STAT3, was greatly diminished Comparable proliferative response observed between wild-type contrast, hardly induced subsequent expression, synergistic production impaired Moreover, augmented MHC class I on cells STAT1-dependent manner. These results suggest activates -2, an indispensable IL-27-induced as well proliferation, while STAT3 presumably important proliferation.

参考文章(43)
Mathias Müller, James Briscoe, Carl Laxton, Dmitry Guschin, Andrew Ziemiecki, Olli Silvennoinen, Ailsa G. Harpur, Giovanna Barbieri, Bruce A. Witthuhn, Chris Schindler, Sandra Pellegrini, Andrew F. Wilks, James N. Ihle, George R. Stark, lan M. Kerr, The protein tyrosine kinase JAK1 complements defects in interferon-α/β and -γ signal transduction Nature. ,vol. 366, pp. 129- 135 ,(1993) , 10.1038/366129A0
Qi Chen, Nico Ghilardi, Hua Wang, Thad Baker, Ming-Hong Xie, Austin Gurney, Iqbal S. Grewal, Frederic J. de Sauvage, Development of Th1-type immune responses requires the type I cytokine receptor TCCR Nature. ,vol. 407, pp. 916- 920 ,(2000) , 10.1038/35038103
Hideo Nariuchi, Toshihiko Yoneto, Chrong-Reen Wang, Yasuhiro Takahama, Takayuki Yoshimoto, Seiji Waki, A Pathogenic Role of IL-12 in Blood-Stage Murine Malaria Lethal Strain Plasmodium berghei NK65 Infection Journal of Immunology. ,vol. 160, pp. 5500- 5505 ,(1998)
Maria Laura Belladonna, Jean-Christophe Renauld, Roberta Bianchi, Carmine Vacca, Francesca Fallarino, Ciriana Orabona, Maria Cristina Fioretti, Ursula Grohmann, Paolo Puccetti, IL-23 and IL-12 Have Overlapping, but Distinct, Effects on Murine Dendritic Cells Journal of Immunology. ,vol. 168, pp. 5448- 5454 ,(2002) , 10.4049/JIMMUNOL.168.11.5448
Peter C. HEINRICH, Iris BEHRMANN, Gerhard MÜLLER-NEWEN, Fred SCHAPER, Lutz GRAEVE, INTERLEUKIN-6-TYPE CYTOKINE SIGNALLING THROUGH THE GP130/JAK/STAT PATHWAY Biochemical Journal. ,vol. 334, pp. 297- 314 ,(1998) , 10.1042/BJ3340297
Takayuki Yoshimoto, Masae Furuhata, Sadahiro Kamiya, Masayuki Hisada, Hiroko Miyaji, Yasushi Magami, Koh Yamamoto, Hiromi Fujiwara, Junichiro Mizuguchi, Positive Modulation of IL-12 Signaling by Sphingosine Kinase 2 Associating with the IL-12 Receptor β1 Cytoplasmic Region Journal of Immunology. ,vol. 171, pp. 1352- 1359 ,(2003) , 10.4049/JIMMUNOL.171.3.1352
Toshihiko Yoneto, Seiji Waki, Toshihiro Takai, Yoh-ichi Tagawa, Yoichiro Iwakura, Junichiro Mizuguchi, Hideo Nariuchi, Takayuki Yoshimoto, A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection. Journal of Immunology. ,vol. 166, pp. 6236- 6241 ,(2001) , 10.4049/JIMMUNOL.166.10.6236
Susanne J Szabo, Sean T Kim, Gina L Costa, Xiankui Zhang, C.Garrison Fathman, Laurie H Glimcher, A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. ,vol. 100, pp. 655- 669 ,(2000) , 10.1016/S0092-8674(00)80702-3
Laura Velazquez, Marc Fellous, George R. Stark, Sandra Pellegrini, A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. ,vol. 70, pp. 313- 322 ,(1992) , 10.1016/0092-8674(92)90105-L