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

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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.