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FcRI and FcRIII/CD16 Differentially Regulate Atopic Dermatitis in Mice¹

Georges Abboud^2,*, Delphine Staumont-Sallé^2,*,, Akira Kanda^*, Thomas Roumier^*, Nathalie Deruytter^*, Céline Lavogiez^*, Sébastien Fleury^*, Patrick Rémy^*, Jean-Paul Papin^*, Monique Capron^* and David Dombrowicz^3,*

^* Institut National de la Santé et de la Recherche Médicale Unité 547, Institut Pasteur de Lille, and Université Lille 2, Lille, France; and Department of Dermatology, Centre Hospitalier Régional Universitaire de Lille, Lille, France

The high-affinity IgE receptor FcRI and, in some models, the low-affinity IgG receptor FcRIII/CD16 play an essential role in allergic diseases. In human skin, they are present on APCs and effector cells recruited into the inflamed dermis. FcR is a subunit shared, among other FcRs, by FcRI and CD16 and is essential to their assembly and signal transduction. Using an experimental model reproducing some features of human atopic dermatitis and specific FcR-deficient mice, we have herein delineated the respective contribution of FcRI and FcRIII/CD16 to the pathology. We demonstrate that symptoms of atopic dermatitis are completely absent in FcR-deficient animals but only partially inhibited in either FcRI- or FcRIII/CD16-deficient animals. Absence or attenuation of the pathology is correlated to increased skin expression of regulatory IL-10 and Foxp3. While FcRI controls both Th1 and Th2 skin response, mast cell recruitment into draining lymph nodes and IgE production, CD16 regulates only Th2 skin response, as well as T cell proliferation and IgG1 production. This isotype-specific regulation by the cognate FcR is associated to a differential regulation of IL-4 and IL-21 expression in the draining lymph nodes. FcRI and CD16 thus contribute to atopic dermatitis but differentially regulate immune responses associated with the disease. Targeting both IgE/FcRI and IgG/CD16 interactions might represent an efficient therapeutic strategy for allergic diseases.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Institut National de la Santé et de la Recherche Médicale and from Fondation pour la Recherche Médicale (Nouveaux défis en Allergologie).

² G.A. and D.S.-S. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. David Dombrowicz, Institut National de la Santé et de la Recherche Médicale Unité 547, Institut Pasteur de Lille, 1, rue Prof. Calmette BP245, 59019 Lille Cedex, France. E-mail address: david.dombrowicz{at}pasteur-lille.fr

⁴ Abbreviations used in this paper: AD, atopic dermatitis; AHR, airway hyperreactivity; BAL, bronchoalveolar lavage; DC, dendritic cell; MHC-II, MHC class II; WT, wild type.