FcεRI and FcγRIII/CD16 Differentially Regulate Atopic Dermatitis in Mice

Abstract

The high-affinity IgE receptor FcεRI and, in some models, the low-affinity IgG receptor FcγRIII/CD16 play an essential role in allergic diseases. In human skin, they are present on APCs and effector cells recruited into the inflamed dermis. FcRγ is a subunit shared, among other FcRs, by FcεRI 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 FcεRI and FcγRIII/CD16 to the pathology. We demonstrate that symptoms of atopic dermatitis are completely absent in FcRγ-deficient animals but only partially inhibited in either FcεRI- or FcγRIII/CD16-deficient animals. Absence or attenuation of the pathology is correlated to increased skin expression of regulatory IL-10 and Foxp3. While FcεRI 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. FcεRI and CD16 thus contribute to atopic dermatitis but differentially regulate immune responses associated with the disease. Targeting both IgE/FcεRI and IgG/CD16 interactions might represent an efficient therapeutic strategy for allergic diseases.