Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other γc-dependent cytokines in peripheral T cells
Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other γc-dependent cytokines in peripheral T cells
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DOI：
10.1074/jbc.m303021200
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发表时间：
2003-06-20
影响因子：
4.8
通讯作者：
Alexander, WS
中科院分区：
文献类型：
--
作者：
Cornish, AL;Chong, MM;Alexander, WS
细胞因子信号传导抑制因子1（SOCS - 1）是细胞因子信号传导的重要调节因子。SOCS - 1基因敲除（-/-）小鼠在断奶前死亡，患有以肝脏脂肪变性和坏死为特征的复杂疾病。这种疾病是由干扰素（IFN）γ介导的，因为在SOCS - 1（-/-）IFNγ（-/-）小鼠中未出现新生期死亡。然而，健康的SOCS - 1（-/-）IFNγ（-/-）小鼠的免疫系统失调，CD4∶CD8 T细胞比例降低，T细胞活化的某些方面增强。SOCS - 1（-/-）IFNγ（-/-）小鼠也比野生型和IFNγ（-/-）同类小鼠更早死亡，伴有一系列炎症病症，包括肺炎、肠道浸润和皮肤溃疡，这表明SOCS - 1不仅控制IFNγ信号传导，还控制其他免疫调节因子。本研究表明，来自SOCS - 1缺陷小鼠的T细胞对通过γc受体起作用的细胞因子表现出超敏反应。白细胞介素（IL）2、IL - 4、IL - 7和IL - 15可诱导SOCS - 1表达，并且SOCS - 1缺陷的T细胞在对IL - 2和IL - 4的反应中显示出增殖增加和存活时间延长。此外，与对照组相比，IL - 2诱导SOCS - 1缺陷的T细胞中STAT5磷酸化和CD44表达增加。对γc依赖性细胞因子的超敏反应可能导致异常的T细胞功能，以及在缺乏SOCS - 1的小鼠中观察到的病理变化。
Suppressor of cytokine signaling- 1 ( SOCS- 1) is an essential regulator of cytokine signaling. SOCS-1(-/-) mice die before weaning with a complex disease characterized by fatty degeneration and necrosis of the liver. This disease is mediated by interferon ( IFN) gamma as neonatal mortality fails to occur in SOCS-1(-/-) IFNgamma(-/-) mice. However, the immune system of healthy SOCS-1(-/-) IFNgamma(-/-) mice is dysregulated with a reduced ratio of CD4: CD8 T cells and increases in some aspects of T cell activation. SOCS-1(-/-) IFNgamma(-/-) mice also die before their wild type and IFNgamma(-/-) counterparts with a range of inflammatory conditions including pneumonia, gut infiltration, and skin ulceration, suggesting that SOCS- 1 controls not only IFNgamma signaling, but also other immunoregulatory factors. This study shows that T cells from SOCS- 1- deficient mice display hypersensitivity to cytokines that act through the gammac receptor. SOCS- 1 expression is induced by interleukin ( IL) 2, IL- 4, IL- 7, and IL- 15, and SOCS- 1-deficient T cells show increased proliferation and prolonged survival in response to IL- 2 and IL- 4. Furthermore, IL- 2 induced increased STAT5 phosphorylation and CD44 expression in SOCS- 1- deficient T cells compared with controls. Hypersensitivity to gammac- dependent cytokines may contribute to abnormal T cell function, as well as the pathology observed in mice lacking SOCS- 1.