Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

Abstract

No single murine model fully captures all aspects of the AD profile; instead, each model reflects different immune or barrier disease aspects. Overall, among the 6 murine models, IL-23-injected mice best simulate human AD; still, the translational focus of the investigation should determine which model is most applicable.

Combined treatment with H1 and H4 receptor antagonists reduces inflammation in a mouse model of atopic dermatitis

“…In the OVA model, the epidermal thickening is less intense in H4R knockout mice, but not in mice treated with an H4R antagonist alone (10). The lack of effect of an H4R antagonist was confirmed in this study, and also the H1R antagonist alone did not affect the thickness of the epidermis.…”

“…In this study, the OVA-challenged model had significant overlap with genes upregulated in human AD but does not capture the downregulated signature of human AD [10]. However, no single murine model fully captured all aspects of the AD profile and each model reflects different immune or barrier disease aspects [10]. Caution should be exercised before translation of murine data to human [10].…”

“…A recent study evaluated the transcriptomic profiles of six common murine skin inflammation models (NC/Nga, flaky tail, Flg-mutated, OVA-challenged (sensitization and provocation procedure not described in the study), Oxazolone -challenged, and IL-23-injected mice) and determined how they related to human AD skin [10]. In this study, the OVA-challenged model had significant overlap with genes upregulated in human AD but does not capture the downregulated signature of human AD [10].…”

“…However, no single murine model fully captured all aspects of the AD profile and each model reflects different immune or barrier disease aspects [10]. Caution should be exercised before translation of murine data to human [10].…”

Interleukin 6 regulates psoriasiform inflammation–associated thrombosis

“…Differences in model systems may account for the different outcomes, such that IL-23 and imiquimod psoriasiform models are acute and elicited, whereas KC-Tie2 and K5-IL-17C models are chronic and occur spontaneously in response to transgene overexpression. Recent work also now suggests that intradermal IL-23-mediated epidermal hyperplasia may more closely reflect atopic dermatitis (39).…”