Expression of Interleukin-4 in the Epidermis of Transgenic Mice Results in a Pruritic Inflammatory Skin Disease: An Experimental Animal Model to Study Atopic Dermatitis

Abstract

Atopic dermatitis, a common, chronic, inflammatory skin disease that occurs with increasing prevalence, is characterized by hyperactivated cytokines of helper T cell subset 2 and is frequently associated with staphylococcal infection. An experimental animal model of atopic dermatitis induced by transgenically introduced cytokine is not available. We generated a transgenic mouse line expressing epidermal interleukin-4, a critical cytokine of helper T cell subset 2. Here we show that transgenic mice spontaneously developed a pruritic inflammatory skin disease reproducing all key features of human atopic dermatitis, including xerosis, conjunctivitis, inflammatory skin lesions, Staphylococcus aureus infection, histopathology of chronic dermatitis with T cell, mast cell, macrophage-like mononuclear cell, and eosinophil infiltration, and elevation of total serum IgE and IgG1. The onset and early progression of skin disease coincided with increased total serum IgE and IgG1. The mouse disease occurred at a 43% annual incidence rate and primarily affected the poorly haired skin: ear (100%), neck (65%), eye (53%), face (29%), tail (12%), leg (12%), and torso (6%). As a group the affected transgenic mice manifested with a skin disorder that fulfilled the clinical diagnostic criteria established for atopic dermatitis in human patients. Pending further characterization to authenticate it as a model of atopic dermatitis, this experimental animal model of pruritic inflammatory skin disease may facilitate investigations for the roles of interleukin-4 in cutaneous inflammation and skin infection in human patients.

IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function

“…Basophils produce large amounts of IL-4 after FcRI ligation (Sullivan et al, 2011), and overexpression of IL-4 is sufficient to drive eosinophilic skin inflammation (Chan et al, 2001). Although sensitized and DNFB-challenged C57BL/6 IL-4 +/ mice developed tissue eosinophilia comparable with wildtype mice, IL-4 / mice (KN2/KN2) had no eosinophil accumulation (Fig.…”

Cutaneous exposure to clinically-relevant pigeon pea (Cajanus cajan) proteins promote TH2-dependent sensitization and IgE-mediated anaphylaxis in Balb/c mice

“…It has been reported that skin of transgenic mice over-expressing IL-4 developed lesions, suggesting that IL-4 may be critical for development of skin lesions (Chan et al 2001). Accordingly, the current study also analyzed mRNA expression of T H 2 cytokines in skin (and intestine) and found elevated levels of IL-4, IL-5 and IL-13 in both sites of EC as well as orally-treated mice.…”

Angiogenesis in cutaneous disease: Part II

“…An epidermal IL-4etrans-genic mouse model was developed that closely resembles human AD clinically, histopathologically, serologically, bacteriologically, and immunologically. [138][139][140][141] The dermal blood vessels in this mouse model show changes consistent with angiogenesis, including elongation, sprouting, and intussusception. 142 Chen et al 143 recently noted a progressive increase in blood vessel number, diameter, and percent dermal area occupied by CD31 1 and VEGFR2 vessels as the disease evolves from start to a chronic state.…”