Hosogi Miwa, Tonogaito Hiroshi, Aioi Akihiro, Hamada Kazuhiko, Shimoda Kazuya, Muromoto Ryuta, Matsuda Tadashi, Miyachi Yoshiki
Biochemistry Laboratory, Pias Corporation, 1-3-1 Murotani, Nishi-ku, Kobe 651-2241, Japan.
J Dermatol Sci. 2004 Oct;36(1):51-6. doi: 10.1016/j.jdermsci.2004.07.007.
Previous studies have shown that Tyk2, a member of the Janus family of protein tyrosine kinases, which are activated by a variety of cytokines, plays a crucial role in interleukin (IL)-12-mediated T-cell functions such as IFN-gamma production. On the other hand, hapten-induced contact hypersensitivity (CHS) is mediated by IFN-gamma producing CD8+ T cells and regulated by CD4+ T cells.
This study hypothesized that the CHS response might be reduced in Tyk2-deficient mice because of a lack of IFN-gamma production from CD4+ and CD8+ T cells.
The CHS reaction was evoked in wild-type and Tyk2-deficient mice and the ears of the mice were examined to measure for several cytokines.
Ear swelling during CHS was significantly enhanced in Tyk2-deficient mice compared with the controls. IL-12 and IFN-gamma levels at the reaction sites in Tyk2-deficient mice were significantly lower than in the controls, whereas IL-2 and IL-4 levels were elevated. Furthermore, STAT3- and STAT4-phosphorylation in the draining lymph node cells of Tyk2-deficient mice decreased.
These results suggest that the lack of Tyk2-mediated signal transduction enhances a compensative pathway during CHS.
先前的研究表明，酪氨酸激酶2（Tyk2）是Janus蛋白酪氨酸激酶家族的成员，可被多种细胞因子激活，在白细胞介素（IL）-12介导的T细胞功能（如γ干扰素产生）中起关键作用。另一方面，半抗原诱导的接触性超敏反应（CHS）由产生γ干扰素的CD8+T细胞介导，并受CD4+T细胞调节。
本研究假设，由于CD4+和CD8+T细胞缺乏γ干扰素产生，CHS反应在Tyk2缺陷小鼠中可能会减弱。
在野生型和Tyk2缺陷小鼠中诱发CHS反应，并检查小鼠耳朵以检测几种细胞因子。
与对照组相比，Tyk2缺陷小鼠CHS期间的耳部肿胀明显增强。Tyk2缺陷小鼠反应部位的IL-12和γ干扰素水平明显低于对照组，而IL-2和IL-4水平升高。此外，Tyk2缺陷小鼠引流淋巴结细胞中的信号转导和转录激活因子3（STAT3）及信号转导和转录激活因子4（STAT4）磷酸化减少。
这些结果表明，Tyk2介导的信号转导缺失增强了CHS期间的补偿途径。
