IL-4 has been implicated to play an important role in the pathogenesis of many inflammatory diseases including skin diseases such as atopic dermatitis. Because it is not clear which pathologic features of atopic dermatitis are dependent on IL-4, we assessed the consequences of IL-4 overexpression in the skin, using transgenic mice overexpressing IL-4 ubiquitously. Although transgenic mice display no clinical signs of skin inflammation, IL-4 induced a wide spectrum of pathologies including an increased number of mast cells and Langerhans cells in dermis and epidermis, respectively, focal deposition of collagen and a considerably reduced adipocyte layer in the dermis as well as an increased mitotic activity of keratinocytes, reflected in acanthosis and hyperkeratosis. The increase in Langerhans cell number may be explained in part by the substantially reduced Langerhans cell emigration from the epidermis in transgenic mice. The molecular mechanism behind this phenomenon remains to be clarified. Under in vitro culture conditions, Langerhans cells from transgenic mice undergo a maturation process similar to that of Langerhans cells from control mice, and their immunostimulatory capacity is also comparable. In contrast, transgenic Langerhans cells are superior to control Langerhans cells in their antigen-processing capacity. We conclude that the overexpression of IL-4 in the skin is, by itself, not sufficient for the induction of a full-blown atopic dermatitis phenotype, but several changes seen in the skin of transgenic mice mirror the cardinal pathologic manifestations of this disease.
While the skin of most patients with atopic dermatitis (AD) is known to contain IgE-bearing cells, the contribution of the various IgE-binding structures to this phenomenon is not fully understood. To address this issue, we eluted cell-bound IgE from cryostat sections of lesional AD skin by acid treatment and performed reconstitution experiments with IgE in the absence or presence of reagents directed against the currently known IgE-binding structures. We found that incubation of acid-treated sections, with either chimeric or serum IgE, resulted in the appearance of sizable numbers of anti-IgE-reactive cells. This cellular IgE loading could be entirely prevented by preincubation of the sections with the anti-Fc epsilonRI alpha MoAb 15-1 but not with either antibodies against Fc epsilonRII/CD23 and Fc gammaRII/CD32 or with alpha-lactose. To exclude the possibility that acid treatment of tissue sections may have adversely influenced the IgE-binding capacity of IgE receptors other than Fc epsilonRI, we performed an identical series of experiments on AD skin samples that, as an exception, were essentially devoid of anti-IgE-reactive cells. Again, no IgE loading was detected when these sections were preincubated with anti-Fc epsilonRI alpha MoAbs. In contrast, preincubation of the sections with alpha-lactose and/or MoAbs against Fc epsilonRII/CD23 or Fc gammaRII/CD32 did not affect IgE loading. Together with the observations that anti-Fc epsilonRI alpha-reactive and IgE-binding cells are largely overlapping populations and include cells of the Langerhans cell/dendritic cell lineage, mast cells, and a few dermal dendrocytes and eosinophils, our results demonstrate that Fc epsilonRI is the predominant and, perhaps, the only biologically relevant IgE-binding structure on histogenetically and functionally diverse cell populations of AD skin.
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