Mechanisms in Allergic Contact Dermatitis

Abstract

Allergic Contact Dermatitis is the consequence of a dysregulated immune response to chemically reactive small molecules, the haptens, penetrating the skin. In the sensitization phase, haptens activate the innate immune system by interacting with pattern recognition receptors, such as Toll like receptors, expressed by skin resident cells, thus initiating a cascade of events leading to the maturation and mobilization of skin dendritic cells. Maturing dendritic cells leave the skin and carry the newly formed hapten epitopes to regional lymph nodes, where they expand a variety of hapten-specific T lymphocytes with the capacity to recirculate in the skin environment. Expression of allergic contact dermatitis is mostly dependent on the recruitment at the site of hapten challenge of hapten-specific CD4+ and CD8+ T cells that, once activated, release pro-inflammatory cytokines and induce the apoptosis of keratinocytes. Contact sensitization is negatively regulated through several mechanisms, including specialized subsets of T regulatory cells, B cells and IL-10-releasing NKT cells, that are both responsible for the development of specific immune tolerance in non-allergic individuals, and limit the magnitude of the inflammatory response during allergic contact dermatitis reactions.