Hyperproduction of proinflammatory Cytokines by WSX-1-deficient NKT cells in concanavalin A-induced hepatitis
Hyperproduction of proinflammatory Cytokines by WSX-1-deficient NKT cells in concanavalin A-induced hepatitis
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DOI：
10.4049/jimmunol.172.6.3590
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发表时间：
2004-03-15
影响因子：
4.4
通讯作者：
Yoshida, H
中科院分区：
文献类型：
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作者：
Yamanaka, A;Hamano, S;Yoshida, H
Con A的给药诱导肝损伤，其被认为是人类自身免疫性或病毒性肝炎的实验模型，其中炎症病理学发挥由活化的淋巴细胞（特别是NK 1.1（+）CD 3（+）NKT细胞）和炎性细胞因子（包括IFN-γ和IL-4）介导的作用。在本研究中，我们利用WSX-1基因敲除小鼠研究了WSX-1（IL-27 R的一种成分）在Con A诱导的肝炎中的作用。WSX-1缺陷型小鼠比野生型小鼠更容易受到Con A治疗，表现出血清丙氨酸转氨酶升高和肝脏大面积坏死。虽然在WSX-1基因敲除小鼠中NKT细胞的发育似乎正常，但在体外和体内对Con A刺激的反应中，来自敲除小鼠的纯化NKT细胞产生的IFN-γ和IL-4比来自野生型小鼠的更多。此外，在Con A给药后，在敲除小鼠中观察到促炎细胞因子（包括IL-1、IL-6和TNF-α）的过度产生。这些数据揭示了WSX-1作为Con A诱导的肝炎中细胞因子产生和炎症的抑制性调节剂的新作用。
Administration of Con A induces liver injury that is considered to be an experimental model for human autoimmune or viral hepatitis, where inummopathology plays roles mediated by activated lymphocytes, especially NK1.1(+) CD3(+) NKT cells, and inflammatory cytokines, including IFN-gamma and IL-4. In the present study we investigated the role of WSX-1, a component of IL-27R, in Con A-induced hepatitis by taking advantage of WSX-1 knockout mice. WSX-1-deficient mice were more susceptible to Con A treatment than wild-type mice, showing serum alanine aminotransferase elevation and massive necrosis in the liver. Although the development of NKT cells appeared normal in WSX-1 knockout mice, purified NKT cells from the knockout mice produced more IFN-gamma and IL-4 than those from wild-type mice in response to stimulation with Con A both in vitro and in vivo. In addition, hyperproduction of proinflammatory cytokines, including IL-1, IL-6, and TNF-alpha, was observed in the knockout mice after Con A administration. These data revealed a novel role for WSX-1 as an inhibitory regulator of cytokine production and inflammation in Con A-induced hepatitis.