Abstracts
Résumé
L’eczéma allergique de contact est une dermatose inflammatoire fréquente, due à l’activation de lymphocytes T (LT) CD8+ cytotoxiques spécifiques d’haptènes en contact avec la peau. Les LT CD4+ sont, quant à eux, doués d’une fonction régulatrice et tolérogène, puisqu’ils limitent l’inflammation cutanée chez les patients (régulation) et préviennent le développement des LT effecteurs chez les individus sains (tolérance) : l’eczéma correspond donc à une rupture de la tolérance immunitaire aux haptènes présents dans l’environnement quotidien. Plusieurs sous-populations de LT CD4+ régulateurs (LT reg), parmi lesquelles celle des LT CD4+CD25+ naturels, sont impliquées dans la tolérance et la régulation de l’eczéma, via la production des cytokines immunosuppressives IL-10 (interleukine-10) et TGFβ (transforming growth factor β). Les travaux en cours ont pour objectif de ré-induire une tolérance immunitaire dans l’eczéma, soit en améliorant les méthodes existantes d’induction de tolérance aux haptènes (tolérance orale, tolérance à faibles doses, immunothérapie spécifique, tolérance induite par les rayons ultraviolets), soit en développant de nouvelles molécules capables d’activer les LT reg. Plus généralement, les données issues de ces travaux devraient pouvoir être appliquées au traitement des maladies auto-immunes ou allergiques, caractérisées par un déficit fonctionnel ou quantitatif en Ltreg à l’origine d’une rupture de la tolérance aux auto-antigènes ou aux allergènes de l’environnement.
Summary
Allergic contact dermatitis (ACD) is a skin inflammatory disease mediated by activation of CD8+ cytotoxic T cells specific for haptens in contact with the skin. CD4+ T cells behave as both regulatory and tolerogenic cells since they down-regulate the skin inflammation in patients with ACD (regulation) and prevent the developement of eczema (tolerance) in normal individuals. Thus, ACD corresponds to a breakdown of immune tolerance to haptens in contact with the skin. Several regulatory CD4+ T cell subsets (Treg), especially CD4+CD25+ natural Treg cells, are involved in immunological tolerance and regulation to haptens through the production of the immunosuppressive cytokines IL-10 and TGF-β. Ongoing strategies to re-induce immune tolerance to haptens in patients with eczema include improvement of existing methods of tolerance induction (oral tolerance, low dose tolerance, allergen-specific immunotherapy, UV-induced tolerance) as well as development of new drugs able to activate IL-10 producing Treg cells in vivo. Ongoing and future progress in this area will open up new avenues for treatment of eczema and more generally autoimmune and allergic diseases resulting from a breakdown of tolerance to autoantigens and allergens, respectively.
Appendices
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