JNK1 is required for T cell-mediated immunity against Leishmania major infection
JNK1 is required for T cell-mediated immunity against Leishmania major infection
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DOI：
10.4049/jimmunol.165.5.2671
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Flavell, RA
中科院分区：
文献类型：
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作者：
Constant, SL;Dong, C;Flavell, RA
c-Jun n-末端激酶（JNK）是一种丝裂原激活的蛋白激酶，在辅助性T细胞分化中起重要的调节作用。在目前的研究中，我们使用jnk1缺陷小鼠来检测JNK在体内致病性感染——利什曼病中的功能，这种感染受到Th1/Th2效应机制的强烈影响。数据显示，Jnk1缺陷小鼠，尽管它们通常具有遗传抗性背景，但仅仅不能解决利什曼原虫感染，Jnk1（-/-）小鼠对病原体的反应显示出延迟型超敏反应减少，这与T细胞缺陷有关。我们发现，尽管这些小鼠可以指导明显的th1反应，但也同时产生利什曼特异性Th2反应，这可能下调th1介导的保护性免疫功能。这些发现表明，JNK1信号通路对Th2细胞因子产生的负调控对于产生针对细胞内病原体（如利什曼原虫）的th1极化免疫至关重要。
c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase that plays important regulatory roles in helper T cell differentiation. In the current study, we used Jnk1-deficient mice to examine the function of JNK during an in vivo pathogenic infection, leishmaniasis, which is strongly influenced by Th1/Th2 effector mechanisms. The data show that Jnk1-deficient mice, despite their usually genetically resistant background, mere unable to resolve Leishmania infections, Jnk1(-/-) mice displayed reduced delayed-type hypersensitivity in response to the pathogen, which was associated with a T cell defect,We found that, although these mice can direct an apparent Th1-response, there is also simultaneous generation of Leishmania-specific Th2 responses, which possibly down-modulate protective Th1-mediated immune function. These findings demonstrate that the negative regulation of Th2 cytokine production by the JNK1 signaling pathway is essential for generating Th1-polarized immunity against intracellular pathogens, such as Leishmania major.