FcεRI and FcγRIII/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 gamma RIII/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 gamma 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 RI and Fc gamma RIII/CD16 to the pathology. We demonstrate that symptoms of atopic dermatitis are completely absent in FcR gamma-deficient animals but only partially inhibited in either Fc epsilon RI- or Fc gamma RIII/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 IgG I 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 RI and 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. The Journal of Immunology, 2009, 182: 6517-6526.