Fc(epsilon)RI and FcgammaRIII/CD16 differentially regulate atopic dermatitis in mice.
The high-affinity IgE receptor Fc(epsilon)RI and, in some models, the low-affinity IgG receptor Fc(epsilon)RIIII/CD16 play an essential role in allergic diseases. In human skin, they are present on APCs and effector cells recruited into the inflamed dermis. FcRgamma is a subunit shared, among other FcRs, by Fc(epsilon)RI 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 Fc(epsilon)RIand Fc(epsilon)RIII/CD16 to the pathology. We demonstrate that symptoms of atopic dermatitis are completely absent in FcRgamma-deficient animals but only partially inhibited in either Fc(epsilon)RI- or FcgammaRIII/CD16-deficient animals. Absence or attenuation of the pathology is correlated to increased skin expression of regulatory IL-10 and Foxp3. While Fc(epsilon)RI 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. Fc(epsilon)RIand CD16 thus contribute to atopic dermatitis but differentially regulate immune responses associated with the disease. Targeting both IgE/Fc(epsilon)RI and IgG/CD16 interactions might represent an efficient therapeutic strategy for allergic diseases.
Abboud
Georges
G
Institut National de la Santé et de la Recherche Médicale Unité 547, Institut Pasteur de Lille, and Université Lille 2, Lille, France.
Staumont-Sallé
Delphine
D
Kanda
Akira
A
Roumier
Thomas
T
Deruytter
Nathalie
N
Lavogiez
Céline
C
Fleury
Sébastien
S
Rémy
Patrick
P
Papin
Jean-Paul
JP
Capron
Monique
M
Dombrowicz
David
D
D000485:Allergens / Q000276:immunology / Q000633:toxicity; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000276:immunology; D007150:Immunohistochemistry; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000485:Allergens; C521907:Fc-epsilon receptor I beta-chain, mouse; C485700:Fcgr3 protein, mouse; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E; D010047:Ovalbumin