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.
Weiss
D L
DL
Department of Chemistry, Williams College, Williamstown, Massachusetts, USA.
Brown
M A
MA
D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D007438:Introns / Q000235:genetics; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008957:Models, Genetic; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009928:Organ Specificity; D012045:Regulatory Sequences, Nucleic Acid; D018418:Th2 Cells / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D015847:Interleukin-4