The role of transcription factors in allergic inflammation

Abstract

The induction of allergic inflammation and the expression of allergic disorders are dependent on the coordinated regulation of numerous genes. The products of these genes determine lymphocyte phenotype, immunologic responsiveness, eosinophil and mast cell development, activation, migration and life span, adhesion molecule expression, cytokine synthesis, cell-surface receptor display, and processes governing fibrosis and tissue repair. Although the expression of gene products involved in these processes is regulated at multiple levels (eg, transcription, mRNA processing, translation, phosphorylation, and degradation), transcription represents an essential and often the most important determinant of their contribution to cellular function. Signal-dependent and cell type-specific regulation of gene expression is generally achieved by means of combinatorial interactions between sequence-specific transcription factors that recruit chromatin remodeling machinery and general transcription factors to promoter and enhancer regions of RNA polymerase II-dependent genes. As targets of signal-transduction pathways, transcription factors integrate the response of the cell to the myriad of inputs it receives. This integration can be accomplished by the effect of signaling cascades on the activation status or subcellular locus of transcription factors or by transcription factor dimerization induced by means of ligand binding. This review will identify the major families of transcription factors important in allergic mechanisms and discuss their interactions, their mechanisms of action, and their interrelated and competitive actions, as well as implications for therapy of allergic disorders.