Naka T, Tsutsui H, Fujimoto M, Kawazoe Y, Kohzaki H, Morita Y, Nakagawa R, Narazaki M, Adachi K, Yoshimoto T, Nakanishi K, Kishimoto T
Department of Molecular Medicine, Osaka Graduate School of Medicine, Suita City, Osaka, Japan.
Immunity. 2001 May;14(5):535-45. doi: 10.1016/s1074-7613(01)00132-7.
Suppressor of cytokine signaling-1 (SOCS-1), also known as STAT-induced STAT inhibitor-1 (SSI-1), is a negative feedback molecule for cytokine signaling, and its in vivo deletion induces fulminant hepatitis. However, elimination of the STAT1 or STAT6 gene or deletion of NKT cells substantially prevented severe hepatitis in SOCS-1-deficient mice, while administration of IFN-gamma and IL-4 accelerated its development. SOCS-1 deficiency not only sustained IFN-gamma/IL-4 signaling but also eliminated the cross-inhibitory action of IFN-gamma on IL-4 signaling. These results suggest that SOCS-1 deficiency-induced persistent activation of STAT1 and STAT6, which would be inhibited by SOCS-1 under normal conditions, may induce abnormal activation of NKT cells, thus leading to lethal pathological changes in SOCS-1-deficient mice.
细胞因子信号转导抑制因子1（SOCS-1），也被称为信号转导和转录激活因子诱导的信号转导抑制因子1（SSI-1），是细胞因子信号转导的负反馈分子，其在体内的缺失会诱发暴发性肝炎。然而，消除STAT1或STAT6基因或缺失NKT细胞可在很大程度上预防SOCS-1缺陷小鼠发生严重肝炎，而给予干扰素-γ和白细胞介素-4则会加速其发展。SOCS-1缺陷不仅使干扰素-γ/白细胞介素-4信号持续存在，还消除了干扰素-γ对白细胞介素-4信号的交叉抑制作用。这些结果表明，SOCS-1缺陷诱导的STAT1和STAT6持续激活（在正常条件下会被SOCS-1抑制）可能会诱导NKT细胞异常激活，从而导致SOCS-1缺陷小鼠出现致命的病理变化。
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