Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation
Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation
复制标题
DOI：
10.1182/blood-2006-11-059246
复制
发表时间：
2007-07-15
期刊：
影响因子：
20.3
通讯作者：
Nakajima, Hiroshi
中科院分区：
文献类型：
--
作者：
Tokumasa, Naoki;Suto, Akira;Nakajima, Hiroshi
有充分证据表明，树突状细胞（dc）是典型的抗原呈递细胞，是th1促进细胞因子的重要来源，并积极参与t辅助细胞分化的调节。然而，调控这一过程的细胞内事件在很大程度上仍是未知的。在这项研究中，我们检测了Tyk2在DC功能中的作用，Tyk2是一种参与IL-12和IL-23信号通路的JAK激酶。虽然Tyk2（-/-）缺失小鼠dc的分化和成熟正常，但il -12诱导的Stat4磷酸化在Tyk2(-/-) dc中减弱。il -12诱导的Tyk2(-/-) dc中IFN-T的产生也显著减少到与Stat4(-/-) dc相似的水平。有趣的是，Tyk2(-/-) dc在CpG ODN刺激下产生IL-12和IL-23的缺陷。此外，Tyk2(-/-) dc诱导Th1细胞分化的能力受损，但不诱导th2细胞分化。综上所述，这些结果表明Tyk2在dc中的表达对于从dc中产生促进th1的细胞因子如IL-12和ifn - γ至关重要，因此对于诱导抗原特异性th1细胞分化至关重要。
It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper-cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2(-/-)) mice, IL-12-induced Stat4 phosphorylation was diminished in Tyk2(-/-) DCs. IL-12-induced IFN-T production was also significantly diminished in Tyk2(-/-) DCs to levels similar to those in Stat4(-/-) DCs. Interestingly, Tyk2(-/-) DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2(-/-) DCs were impaired in their ability to induce Th1 -cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-gamma from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.