Analysis of Txk functions in the development of Th1 cells and its application for treatment of autoimmune and allergic diseases

辅助性T细胞1型（Th1）和Th2细胞分别由白细胞介素(IL)-12和IL-4存在下的抗原刺激产生，与包括过敏性和自身免疫性疾病在内的疾病病理有关。Txk/Rlk是Tec家族酪氨酸激酶的一员。我们已经报道了Txk在T淋巴细胞中作为Th1细胞特异性转录因子。我们发现，Txk的表达受IL-12、IL-18和IFN-g的正向影响，而受IL-4和IL-13的负向影响。接下来，我们研究了txk表达质粒是否能诱导小鼠脾细胞中txk的表达。与以抗原特异性方式给予对照质粒的小鼠相比，给予txk表达质粒的小鼠脾脏细胞产生更多的ifn - γ。两组小鼠脾细胞IL-2和IL-4分泌量具有可比性。Txk未降低血清IgG浓度。然而，它显著降低了血清总IgE水平和IgG1/IfG2a比率，反映了Th1/Th2平衡。此外，给药txk降低了小鼠血清中抗原特异性IgE水平，用于免疫小鼠。因此，Txk增强IFN-g的分泌，从而调节Th1/Th2细胞因子的平衡，从而在体内以抗原特异性的方式降低血清IgE。

T helper type 1 (Th1) and Th2 cells, resulting from antigenic stimulation in the presence of interleukin (IL)-12 and IL-4, respectively, are implicated in the pathology of diseases including allergic and autoimmune diseases.Txk/Rlk is a member of Tec family tyrosine kinases. We have reported that Txk acts as a Th1 cell specific transcription factor in the T lymphocytes. We found that Txk expression was affected positively by IL-12, IL-18 and IFN-g and negatively by IL-4 and IL-13.We next studied whether administration of txk expression plasmid induced expression of Txk in their spleen cells. The spleen cells from the mice administered txk expression plasmid produced more IFN-gamma as compared with those from mice administered control plasmid in an antigen specific manner. IL-2 and IL-4 secretion of the spleen cells were comparable between the two mouse groups. Txk administration did not reduce serum IgG concentration.However, it markedly reduced serum total IgE level and an IgG1/IfG2a ration, reflection of Th1/Th2 balance. Furthermore, txk administration reduced the antigen specific IgE levels in sera of the mice, which was used for immunizing mice. Thus, Txk enhances IFN-g secretion and thus modulates Th1/Th2 cytokine balance, leading to reduction of serum IgE in an antigen specific manner in vivo.