How are Epidermal Langerhans Cells Activated in the Initiation Phase of Allergic Contact Dermatitis?

Setsuya Aiba
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan

AATEX 11(1):49-58, 2005

In the allergic contact hypersensitivity, the chemical penetrates into the viable layers of the epidermis and into the various cells therein. At these sites, the chemical must react with carrier protein or peptide to form a T cell epitope as well as activate Langerhans cells (LC). The reaction of haptens with proteins is either covalent or non-covalent, such as by forming a coordination complex. Meanwhile, hap-tens activate LC. Although the mechanism by which hapten activates LC is still controversial, it is accepted that LC must be activated in the initiation phase of allergic contact hypersensitivity reaction. The activated LC with augmented expression of various costimulatory molecules and increased production of proinflammatory cytokines start to migrate via the afferent lymphatics to the draining lymph nodes where they present hapten to naive T cells. To migrate to the lymph nodes, LC downregulate E-cadherin which functions in anchoring LC in the epidermis, produce MMP-9 that is required for passing through the basement membrane, and increase their expression of chemokine receptor CCR7 that induces the migration toward CCL-19 (MIP-3b) and CCL-21 (SLC). Our current and ultimate challenge is developing non-animal test methods which can predict a chemical's skin sen-sitization potential in vitro. For that purpose, it is crucial to understand the mechanism of allergic contact hypersensitivity, especially, its initiation phase. In this review, I have focused on the current understanding regarding the mechanism of activation of LC in the initiation phase.

Key words:hapten, Langerhans cell, contact dermatitis,redox, p38 mitogen-activated protein kinase


(AATEX: Altern. Animal Test. EXperiment.: Alternatives to Animal Testing and EXperimentation)