Gene expression profiling in allergic contact dermatitis

Abstract

The successful acquisition of skin sensitisation requires orchestrated cellular and molecular interactions that collectively result in the induction of a cutaneous immune response of the required quality and vigour. Pivotal roles are played by epidermal Langerhans cells (LC), and by the mature immunostimulatory dendritic cells (DC) into which they mature. LC serve as sentinels of the adaptive immune system with responsibility for surveying changes in the local microenvironment and for processing antigen (and chemical allergens) encountered at skin surfaces. Following such encounters LC are mobilised and stimulated to migrate, via afferent lymphatics, to regional lymph nodes. While in transit they lose the properties of antigen processing cells and acquire instead the characteristics of mature DC that are able to interact effectively with, and present antigen to, T lymphocytes. To gain a greater understanding of the molecular events that induce and regulate cutaneous immune responses to chemical allergens, we have used microarray transcript profiling and related experimental approaches to characterise changes in gene expression and protein production associated with the development of skin sensitisation. Our attention has focused particularly on changes in the expression of mRNA and protein resulting from the interaction of chemical allergens with DC, and associated with the presentation of antigen to T lymphocytes.