Gene expression patterns and susceptibility to allergic responses.
Allergic diseases are due to hypersensitive immune responses against otherwise innocuous allergens, and involve the dysregulated expression of numerous genes in cells from both the innate and adaptive immune systems. Allergic diseases are characterized by the enhanced production of type 2 T helper (Th2) cytokines, including interleukin-4, -5 and -13. These cytokines induce many of the pathophysiologic hallmarks of allergy, and their expression is tightly regulated at the level of gene transcription by both positively and negatively-acting transcription factors. In this review, the authors summarize data indicating that some of these factors represent checkpoints in the development of allergic diseases. Th2 gene expression is also controlled at the level of chromatin remodeling, and the implications of chromatin-based Th2 gene regulation in allergic disorders is also discussed. The differentiation of Th2 cells from naive precursors is critically dependent upon instruction received from dendritic cells, although the precise signals involved in this process are not well understood. Current thinking regarding some of the environmental cues interpreted by dendritic cells during allergen encounter, and how they promote Th2 responses will be reviewed. Understanding the cross-talk between dendritic cells and T cells holds great promise for deciphering the dysregulated immune response in allergy.
Williams
Marc
M
Johns Hopkins Asthma & Allergy Center, 5501 Hopkins Bayview CircleBaltimore, MD 21224, USA. mwilli35@jhmi.edu
Georas
Steve
S