A regulatory role for suppressor of cytokine signaling-1 in T sub(h) polarization in vivo

• Published in: International immunology Vol. 14; no. 11; pp. 1343 - 1350
• Main Authors: Fujimoto, Minoru, Tsutsui, Hiroko, Yumikura-Futatsugi, Shizue, Ueda, Haruyasu, Xingshou, Ouyang, Abe, Tatsuo, Kawase, Ichiro, Nakanishi, Kenji, Kishimoto, Tadamitsu, Naka, Tetsuji
• Format: Journal Article
• Language: English
• Published: 01.11.2002
• ISSN: 0953-8178

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 super(-/-) mice on an IFN- gamma super(-/-), STAT1 super(-/-) and STAT6 super(-/-) background revealed that the fatal disease of SOCS-1 super(-/-) mice is also dependent on IFN- gamma /STAT1 and IL-4/STAT6 signaling pathways. Since IFN- gamma and IL-4 are representative T sub(h)1 and T sub(h)2 cytokines respectively, here we investigated the role of SOCS-1 in T sub(h) differentiation. Freshly isolated SOCS-1 super(-/-) CD4 super(+) T cells stimulated with anti-CD3 rapidly produced larger amounts of IFN- gamma and IL-4 than control cells, suggesting that these mutant T cells had already differentiated into T sub(h)1 and T sub(h)2 cells in vivo. In addition, SOCS-1 super(+/-) CD4 super(+) T cells cultured in vitro produced significantly larger amounts of IFN- gamma and IL-4 than SOCS-1 super(+/+) cells. Similarly, SOCS-1 super(+/-) CD4 super(+) T cells produced more IFN- gamma and IL-4 than SOCS-1 super(++) 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 super(-/-) T cells, the enhanced T sub(h) functions in SOCS-1 super(-/-) and SOCS-1 super(+/-) mice appear to be due to the enhanced effects of these cytokines. These results suggest that SOCS-1 plays a regulatory role in both T sub(h)1 and T sub(h)2 polarizations.