Establishment and Characterization of Mild Atopic Dermatitis in the DNCB-Induced Mouse Model

Abstract

In dermatological research, 2,4-dinitrochlorbenzene (DNCB)-induced atopic dermatitis (AD) is a standard model as it displays many disease-associated characteristics of human AD. However, the reproducibility of the model is challenging due to the lack of information regarding the methodology and the description of the phenotype and endotype of the mimicked disease. In this study, a DNCB-induced mouse model was established with a detailed procedure description and classification of the AD human-like skin type. The disease was induced with 1% DNCB in the sensitization phase and repeated applications of 0.3% and 0.5% DNCB in the challenging phase which led to a mild phenotype of AD eczema. Pathophysiological changes of the dorsal skin were measured: thickening of the epidermis and dermis, altered skin barrier proteins, increased TH1 and TH2 cytokine expression, a shift in polyunsaturated fatty acids, increased pro-resolving and inflammatory mediator formation, and dysregulated inflammation-associated gene expression. A link to type I allergy reactions was evaluated by increased mast cell infiltration into the skin accompanied by elevated IgE and histamine levels in plasma. As expected for mild AD, no systemic inflammation was observed. In conclusion, this experimental setup demonstrates many features of a mild human-like extrinsic AD in murine skin.

Characterization of Different Inflammatory Skin Conditions in a Mouse Model of DNCB-Induced Atopic Dermatitis

“…While Flg was downregulated in the moderate hlAD lesions at day 12, the expression was upregulated at the end of the experiment, indicating mild hlAD. This finding is in line with the results from the literature, where Flg downregulation is described for DNCB-induced moderate to severe hlAD [ 21 , 60 , 61 ] but not for mild hlAD [ 27 ] or mild human AD [ 62 ]. Krt10, an early differentiation marker, remained unchanged by DNCB treatment in our study.…”

“…In the literature, there is no identifiable correlating parameter described that is responsible either for the maintenance, reduction, or increase of the disease severity until the end of the experiment. Moreover, only a few studies classified the pheno- or endotype of the DNCB-treated murine skin eczema regarding human AD [ 27 ]. Above all, studies are lacking descriptions of the disease severity before starting the therapeutic treatment.…”

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice

“…Our data suggest that the underlying mechanisms A DNCB-induced model of atopic dermatitis (AD) was employed in BALB/c mice due to its close resemblance to the signs of human AD, such as skin erosion, hemorrhage, epidermal hyperplasia, histopathological features of mast cell infiltration, increased levels of serum IgE, and infiltration of inflammatory cells with thickened epidermis and dermis. 27,28 IgE levels are key parameter that has been extensively studied in patients with atopic dermatitis. Approximately 80% of AD patients have been reported to have elevated serum IgE levels.…”

The therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on chemically induced atopic dermatitis

“…Our rst objective was to establish a human-like mouse model of AD using DNCB, which is commonly used to induce chronic AD-like skin lesions 17 . The repeated application of DNCB to mouse skin results in different phases of sensitization and challenge, depending on the dosage used [18][19][20][21] . A human-like AD mouse model was successfully established by applying 1% DNCB during the sensitization phase and 0.4% DNCB during the induction phase to the dorsal skin of mice [18][19][20][21] .…”

“…The repeated application of DNCB to mouse skin results in different phases of sensitization and challenge, depending on the dosage used [18][19][20][21] . A human-like AD mouse model was successfully established by applying 1% DNCB during the sensitization phase and 0.4% DNCB during the induction phase to the dorsal skin of mice [18][19][20][21] . Severe erythema, erosion, and excoriation were observed in the dorsal skin of the DNCB-treated mice (Supplementary Fig.…”