PI3K-mediated negative feedback regulation of IL-12 production in DCs
PI3K-mediated negative feedback regulation of IL-12 production in DCs
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DOI：
10.1038/ni825
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发表时间：
2002-09-01
影响因子：
30.5
通讯作者：
Koyasu, S
中科院分区：
文献类型：
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作者：
Fukao, T;Tanabe, M;Koyasu, S
虽然树突状细胞（DC）产生的白细胞介素12（IL-12）通过调节先天性和适应性免疫来保护机体免受有害的入侵，但其调节异常可能对宿主产生有害影响。我们发现磷酸肌醇3-激酶（PI 3 K）负调控DC合成IL-12。我们发现，许多刺激诱导IL-12的产生伴随着引发PI 3 K激活的DC，但PI 3 K（-/-）和PI 3 K受体处理的DC显示IL-12的产生增加。因此，在PI 3 K（-/-）小鼠中，在感染硕大利什曼原虫后观察到增强的T辅助1型（THI）应答。我们的研究结果表明，存在负反馈机制，调节DC激活过程中IL-12的产生，并可能有助于防止过度THI极化，导致不良的免疫反应。
Although interleukin 12 (IL-12) production by dendritic cells (DCs) confers protection against harmful invasions by regulating both innate and adaptive immunity, its dysregulation may have detrimental effects on the host. We show here that phosphoinositide 3-kinase (PI3K) negatively regulates IL-12 synthesis by DCs. We found that numerous stimuli that induced IL-12 production concomitantly elicited PI3K activation in DCs, but both PI3K(-/-) and PI3K inhibitor-treated DCs showed increased IL-12 production. Accordingly, an enhanced T helper type 1 (THI) response was observed upon Leishmania major infection in PI3K(-/-) mice. Our findings indicate that a negative feedback mechanism exists that regulates IL-12 production during DC activation and may help prevent the excessive THI polarization that causes undesirable immune responses.