We have been studying how cytokines induce gene expression. We previously showed that IL 1 induced IL 2 via the transcription factor AP-1. We now show that the components of AP-1 (jun and fos) are differently regulated in different cell types responding to IL 1. T cells produce only jun in response to IL 1, and need a signal from the antigen receptor to induce fos - thus IL 1 is a cofactor in T cells. Hepatocytes and pituitary cells produce both jun and fos in response to IL 1 - thus IL 1 alone is sufficient to induce many genes via AP-1 in these cells. We are examining the jun promoter for IL 1 responsive elements. Another project deals with T cell receptor (TcR) rearrangement. We have developed a new PCR technique for studying this gene rearrangement process, and are applying it to study the cellular stimuli and intracellular mechanisms of TcR gene rearrangement. A major new direction will be targeting cytokine genes, with the goal of creating mice that lack certain specific cytokines; these will be used to study the in vivo roles of the cytokines.
