Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, McCoy B, Bogdan C, Decker T, Brem G, Pfeffer K, Müller M
Institute of Animal Breeding and Genetics, Veterinary University of Vienna, Austria.
Immunity. 2000 Oct;13(4):549-60. doi: 10.1016/s1074-7613(00)00054-6.
To assess the role of the Janus kinase (Jak) family member Tyk2, we have generated Tyk2-/- mice. In contrast to other Jaks, where inactivation leads to a complete loss of the respective cytokine receptor signal, Tyk2-/- mice display reduced responses to IFNalpha/beta and IL-12 and a selective deficiency in Stat3 activation in these pathways. Unexpectedly, IFNgamma signaling is also impaired in Tyk2-/- mice. Tyk2-/- macrophages fail to produce nitric oxide upon lipopolysaccharide induction. Tyk2-/- mice are unable to clear vaccinia virus and show a reduced T cell response after LCMV challenge. These data imply a selective contribution of Tyk2 to the signals triggered by various biological stimuli and cytokine receptors.
为了评估Janus激酶（Jak）家族成员酪氨酸激酶2（Tyk2）的作用，我们培育出了Tyk2基因敲除小鼠。与其他Jaks不同，其他Jaks失活会导致相应细胞因子受体信号完全丧失，而Tyk2基因敲除小鼠对IFNα/β和IL-12的反应减弱，并且在这些信号通路中Stat3激活存在选择性缺陷。出乎意料的是，Tyk2基因敲除小鼠中的IFNγ信号传导也受损。Tyk2基因敲除的巨噬细胞在脂多糖诱导后无法产生一氧化氮。Tyk2基因敲除小鼠无法清除痘苗病毒，并且在淋巴细胞脉络丛脑膜炎病毒（LCMV）攻击后T细胞反应减弱。这些数据表明Tyk2对各种生物刺激和细胞因子受体触发的信号有选择性贡献。
