Fiche publication
Date publication
octobre 2005
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
,
Dr METZGER Daniel
,
Dr TELETIN Marius
Tous les auteurs :
Li M, Messaddeq N, Teletin M, Pasquali JL, Metzger D, Chambon P
Lien Pubmed
Résumé
To investigate the role of retinoid X receptors (RXRs) in epidermal homeostasis, we generated RXRalphabeta(ep-/-) somatic mutants in which both RXRalpha and RXRbeta are selectively ablated in epidermal keratinocytes of adult mice. These mice develop a chronic dermatitis mimicking that observed in atopic dermatitis (AD) patients. In addition, they exhibit immunological abnormalities including elevated serum levels of IgE and IgG, associated with blood and tissue eosinophilia, indicating that keratinocyte-selective ablation of RXRs also generates a systemic syndrome similar to that found in AD patients. Furthermore, the profile of increased expression of cytokines and chemokines in skin of keratinocyte-selective RXRalphabeta-ablated mutants was typical of a T helper 2-type inflammation, known to be crucially involved in human AD pathogenesis. Finally, we demonstrate that thymic stromal lymphopoietin, whose expression is rapidly and strongly induced in RXRalphabeta-ablated keratinocytes, plays a key role in initiating the skin and systemic AD-like pathologies.
Mots clés
Animals, Cytokines, metabolism, Dermatitis, Atopic, genetics, Genotype, Immunoglobulin E, blood, Immunoglobulin G, blood, Immunohistochemistry, Keratinocytes, metabolism, Mice, Mice, Knockout, Retinoid X Receptors, genetics, Skin, metabolism
Référence
Proc. Natl. Acad. Sci. U.S.A.. 2005 Oct;102(41):14795-800
