Translational Relevance of Mouse Models of Atopic Dermatitis

Abstract

The complexity of atopic dermatitis (AD) continues to present a challenge in the appropriate selection of a mouse model because no single murine model completely recapitulates all aspects of human AD. This has been further complicated by recent evidence of the distinct AD endotypes that are dictated by unique patterns of inflammation involving Th1, Th2, Th17, and Th22 axes. A review of currently used mouse models demonstrates that while all AD mouse models consistently exhibit Th2 inflammation, only some demonstrate concomitant Th17 and/or Th22 induction. As the current understanding of the pathogenic contributions of these unique endotypes and their potential therapeutic roles expands, ongoing efforts to maximize a given mouse model’s homology with human AD necessitates a close evaluation of its distinct immunological signature.

Dendritic cell immunoreceptor drives atopic dermatitis by modulating oxidized CaMKII-involved mast cell activation

“…As expected, cockroach allergen-induced mice showed thickening of the epidermal and dermal layers and infiltration of inflammatory cells. Particularly, these mice displayed increased skin infiltration of Th2, ILC2, and mast cells and elevated Th2 and inflammatory cytokine expression that have been well documented for human AD (3,4,43,49), suggesting that our newly generated mouse model is a useful model to study the allergen-induced pathogenic processes and its underlying mechanisms.…”

“…Subcutaneous allergen immunotherapy has been suggested to be an effective therapeutic approach for AD (59,60), implying that allergen plays a pathogenic role in the development of AD. To better understand the role of cutaneous exposure to aeroallergens in AD, several mouse models of allergen-induced AD-like skin inflammation have been established and recognized as a powerful approach to analyze the allergen-induced pathophysiology of AD and elucidate the underlying mechanisms (43)(44)(45)(61)(62)(63). Of these, the OVA-induced AD mouse model has been well established (43)(44)(45); we therefore used OVA as a positive control to establish a new AD-like mouse model by using cockroach allergen.…”

“…To better understand the role of cutaneous exposure to aeroallergens in AD, several mouse models of allergen-induced AD-like skin inflammation have been established and recognized as a powerful approach to analyze the allergen-induced pathophysiology of AD and elucidate the underlying mechanisms (43)(44)(45)(61)(62)(63). Of these, the OVA-induced AD mouse model has been well established (43)(44)(45); we therefore used OVA as a positive control to establish a new AD-like mouse model by using cockroach allergen. As expected, cockroach allergen-induced mice showed thickening of the epidermal and dermal layers and infiltration of inflammatory cells.…”

“…We first examined whether repetitive topical exposure to cockroach allergen can induce AD-like skin inflammation in a cockroach allergen-induced mouse model of atopic dermatitis modified from previous reports (Fig. 1, A) (43)(44)(45). Cockroach allergen challenge was performed by epicutaneous treatment with 100 µg of cockroach extract (CRE).…”

Extracellular Matrix Remodeling in Atopic Dermatitis Harnesses the Onset of an Asthmatic Phenotype and Is a Potential Contributor to the Atopic March

“…To mimic an atopic march-like process, allergens like house dust mites or ovalbumin are administered via inhalation or s.c. injection t [ 25 ]. Detailed insights about the model’s capability to mimic specific aspects of AD are described elsewhere [ 26, 27 ]. To our knowledge, none of the existing mouse models of AD emulate the whole process of the atopic march from skin to other organs.…”