Regulation of IL-4 production in mast cells: A paradigm for cell-type-specific gene expression

The role of interleukin (IL)-4 as an important immunomodulatory cytokine is well established. IL-4 exhibits a highly restricted pattern of expression by cells of distinct lineages. The cell types that produce IL-4 are located in anatomically distinct locations (e.g. circulating T cells vs. fixed tissue mast cells) and thus have access to different IL-4-responsive target cells. In addition, these cells appear to regulate IL-4 expression in cell-type-specific ways. These findings suggest that an understanding of IL-4 gene regulation in T and mast cells could provide the means to specifically control IL-4 release in a lineage- and site-specific manner. In this article we review the current knowledge regarding the cell-type specific regulation of IL-4 gene expression in mast cells and compare this to what has been defined in T cells. We show that there are distinct yet parallel events that control developmentally determined chromatin modifications, allowing accessibility of the locus, and provide the potential for transcription. In differentiated cells, a subset of unique cell activation signals initiates the cascade of events that lead to transcriptional activation of the IL-4 gene.