Mouse models of atopic dermatitis: a critical reappraisal.
DNCB
hapten
humanized mouse
ovalbumin
oxazolone
Journal
Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
revised:
17
12
2020
received:
09
07
2020
accepted:
17
12
2020
pubmed:
29
12
2020
medline:
25
2
2022
entrez:
28
12
2020
Statut:
ppublish
Résumé
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 suggest that valid AD models should at least meet the following criteria: (a) an AD-like epidermal barrier defect with reduced filaggrin expression along with hyperproliferation, hyperplasia; (b) increased epidermal expression of thymic stromal lymphopoietin (TSLP), periostin and/or chemokines such as TARC (CCL17); (c) a characteristic dermal immune cell infiltrate with overexpression of some key cytokines such as IL-4, IL-13, IL-31 and IL-33; (d) distinctive "neurodermatitis" features (sensory skin hyperinnervation, defective beta-adrenergic signalling, neurogenic skin inflammation and triggering or aggravation of AD-like skin lesions by perceived stress); and (e) response of experimentally induced skin lesions to standard AD therapy. Finally, we delineate why humanized AD mouse models (human skin xenotransplants on SCID mice) offer a particularly promising preclinical research alternative to the currently available "AD" mouse models.
Substances chimiques
Biomarkers
0
Haptens
0
calcipotriene
143NQ3779B
Ovalbumin
9006-59-1
Calcitriol
FXC9231JVH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
319-336Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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