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Summary: 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. This work was supported by the National Science Foundation (DLW), the National Institutes of Health and the Multiple Sclerosis Society (MAB). We appreciate the technical and intellectual contributions of many colleagues including Doris Powell, John Hural, Tammy Nachman, Ben Hock, David Tara, Greg Henkel, Susan Lee, Millie Kwan, Melanie Sherman and Ginny Secor.
Weiss et al. (Thu,) studied this question.