Txk, a Member of Nonreceptor Tyrosine Kinase of Tec Family, Acts as a Th1 Cell-Specific Transcription Factor and Regulates IFN-γ Gene Transcription

Precise mechanisms responsible for Th1 cell activation and differentiation are not fully elucidated. We have recently reported that Txk, a member of Tec family nonreceptor tyrosine kinase, is expressed on Th1/Th0 cells, and Txk regulates specifically IFN-γ gene expression. In this study, we found that Txk bound to IFN-γ promoter region. Txk transfection increased transcriptional activity of IFN-γ promoter plus luciferase constructs severalfold, including IFN-γ promoter −538, −208, and −53. IFN-γ promoter −39 was refractory to the Txk transfection. The actual site to which Txk bound was the element consisting of −53 and −39 bp from the transcription start site of human IFN-γ gene, a site distinct from several previously characterized binding sites. We found that the entire −53/−39 region was necessary for the binding to and function of Txk, because mutant promoter oligoDNA that contained contiguous five base substitutions dispersed throughout the −53/−39 inhibited the binding, and the mutant promoters did not respond to the Txk transfection. Similar sequences of this element are found within the 5′ flanking regions of several Th1 cell-associated protein genes. Thus, Txk is expressed on Th1/Th0 cells with the IFN-γ production and acts as a Th1 cell-specific transcription factor.