344 FcRγ-mediated Immune Responses Modulate the Exacerbation of Clinical Symptoms in Atopic Dermatitis of NC/TND Mice

BACKGROUND: Although elevated specific IgG and IgE are observed in sera of patients with atopic dermatitis (AD), their involvement in the pathogenesis of AD remains to be determined. In this study, we investigated the contribution of the immunoglobulin in AD by using Fc receptor common γ-chain (FcRγ)-deficient NC/Tnd mice. METHODS: NC/Tnd mice spontaneously develop the AD skin lesion when they are raised in air-unregulated conventional circumstances, but not when maintained under air-regulated specific pathogen-free conditions. We established FcRγ - NC/Tnd mice; those mice lacked FcRγ-mediated immune responses initiated by specific IgG and IgE. The clinical skin severity score and scratching behavior were evaluated in FcRγ-deficient mice and wild-type (WT) littermates. To examine histological features and distribution of mast cells, tissue sections of the lesional skin were stained with hematoxylin-eosin and toluidine blue, respectively. With regard to inflammatory cytokine production, the mRNA expression was detected in the dorsal skin and the axillary lymph node by real-time RT-PCR. RESULTS: Although the absence of FcRγ did not affect production of the immunoglobulin, the clinical skin severity scores were lower in FcRγ(-/-) NC/Tnd mice by half than in conventional WT mice. On the other hand, there were no differences in both scratching behavior elicited by dermatitis and Th1/Th2 cytokine production between 2 groups of mice. In the skin lesion of FcRγ null mice, mild epidermal hyperplasia and immune cell infiltration were observed. Particularly, mast cell numbers and their degranulation were significantly decreased in the skin of FcRγ-deficient mice. CONCLUSIONS: FcRγ was not critical to the onset of AD, because FcRγ-deficient mice exhibited moderate dermatitis and scratching behavior comparable to WT. On the other hand, although scratching behavior induced the mechanical destruction of skin barriers and mast cell activation, the absence of FcRγ markedly attenuated the skin severity, immune cell recruitment including lymphocytes, and mast cell degranulation. These results indicated that the FcRγ-mediated immune response by specific IgG and IgE regulate the exacerbation of clinical symptoms in AD.