International Immunology, Vol. 14, No. 11, pp. 1343-1350,
November 2002
© 2002 Japanese Society for Immunology
FEATURED ARTICLE OF THE MONTH |
A regulatory role for suppressor of cytokine signaling-1 in Th polarization in vivo
1 Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2–2 Yamadaoka, Suita City, Osaka 565-0871, Japan 2 Department of Immunology and Medical Zoology, and 3 Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501 Japan 4 Osaka University Graduate School, 1-1 Yamadaoka, Suita City, Osaka 565-0871 Japan 5 Present address: Core Research for Evolutional Science and Technology, Japan Science and Technology Corp., Tokyo 101-0062, Japan
Correspondence to: T. Naka; E-mail: naka{at}imed3.med.osaka-u.ac.jp
Transmitting editor: L. H. Glimcher
Suppressor of cytokine signaling (SOCS)-1 is an inhibitory molecule for JAK, and its deficiency in mice leads to lymphocyte-dependent multi-organ disease and perinatal death. Crossing of SOCS-1–/– mice on an IFN-
–/–, STAT1–/– and STAT6–/– background revealed that the fatal disease of SOCS-1–/– mice is also dependent on IFN-/STAT1 and IL-4/STAT6 signaling pathways. Since IFN- and IL-4 are representative Th1 and Th2 cytokines respectively, here we investigated the role of SOCS-1 in Th differentiation. Freshly isolated SOCS-1–/– CD4+ T cells stimulated with anti-CD3 rapidly produced larger amounts of IFN- and IL-4 than control cells, suggesting that these mutant T cells had already differentiated into Th1 and Th2 cells in vivo. In addition, SOCS-1+/– CD4+ T cells cultured in vitro produced significantly larger amounts of IFN- and IL-4 than SOCS-1+/+ cells. Similarly, SOCS-1+/– CD4+ T cells produced more IFN- and IL-4 than SOCS-1+/+ cells after infection with Listeria monocytogenes and Nippostrongyrus braziliensis respectively. Since IL-12-induced STAT4 and IL-4-induced STAT6 activation is sustained in SOCS-1–/– T cells, the enhanced Th functions in SOCS-1–/– and SOCS-1+/– mice appear to be due to the enhanced effects of these cytokines. These results suggest that SOCS-1 plays a regulatory role in both Th1 and Th2 polarizations.
Keywords: JAK, STAT, STAT-induced STAT inhibitor, suppressor of cytokine signaling-1, Th1, Th2
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