Mouse models of atopic dermatitis: a critical reappraisal

Abstract

Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool for testing new candidate AD therapeutics and for interrogating AD pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so-called "AD" mouse models satisfactorily reflect the clinical complexity of human AD, but imitate more "allergic" or "irriant" contact dermatitis conditions. This limits the predictive value of AD models for clinical outcomes of new tested candidate AD therapeutics and the instructiveness of mouse models for human AD pathophysiology research. Here, we propose to initiate a rational debate on the minimal criteria that a mouse model should meet in order to be considered relevant for human AD. We

Translational Relevance of Mouse Models of Atopic Dermatitis

“…Kim et al (2019) previously outlined several features that warrant consideration in the selection of a mouse model, including gross phenotype/histology, serum profile, transcriptomic similarities, and immunophenotype [6]. More recently, Gilhar et al (2020) proposed a list of criteria that animal models of human AD should meet, which included the consideration of inflammatory patterns [29]. An in-depth assessment of a model's unique immunological signature and the ability to individually modulate specific immune axes may be key for future preclinical studies seeking to assess how novel biologics blockade the inflammatory upregulation that defines specific AD endotypes, as selection based on genetics, phenotype, or gene expression profile may not adequately capture the immunologic complexity of AD.…”

“…Looking to the future, newer techniques such as the bioengineered humanized skin model [17] and the transplantation of stimulated peripheral blood mononuclear cells (PBMC) [29] hold great promise in their potential ability reproduce population-specific immune signatures in mice. While these techniques are further explored and characterized, a more practical approach to improving existing models' translational relevance can be guided by efforts to increase their versatility by exploring modifications that selectively modulate inflammatory responses, such as the use of CMIT/MIT prior to OVA sensitization to bolster Th17 response [36], or by characterizing the inflammatory response demonstrated by different mouse strains to aid in the selection of a model that most closely mimics a desired immune signature [28,37].…”

“…In both cases, a concern lies in the task of capturing the complex features of AD in their entirety, which is further complicated by the lack of consensus regarding the features that define such criteria [29]. Thus, an additional measure to optimize the utility of existing models may involve validating therapies across a heterogenous panel of animal models, taking advantage of the common mediators that underlie cutaneous inflammation in different models.…”

Updated understanding of Staphylococcus aureus in atopic dermatitis: From virulence factors to commensals and clonal complexes

“…CC1 types have been identified as that are non-essential but excellent if met. 164 We discuss elements of their suggested criteria in regard to studying SA in human AD.…”

Recent progress at the psoriasis and atopic dermatitis research front: An experimental dermatology perspective

“…Mouse models for AD or PSO are critical preclinical research tools for the investigation of disease pathobiology and for testing the efficacy and determining the pharmacology of new candidate drugs and other therapeutic interventions. An international consensus paper by Gilhar et al 65 . has raised concerns that the currently available so‐called ‘AD’ mouse models may not sufficiently reflect the clinical complexity of human AD.…”