Several studies have tried to establish mice models of atopic dermatitis (AD) through the allergen of Dermatophagoides farinae (Df). However, there are no typical skin lesions after epicutaneous application of an extract of Df (DfE) on BALB/c mice. Dinitrofluorobenzene (DNFB) is a common hapten that brings about contact dermatitis. Skin dysfunction induced by DNFB may be a way to enhance the effects of DfE on mice skin. Thus, we hypothesized that alternate epicutaneous application of DNFB and DfE could induce AD-like skin lesions on BALB/c mice. To test this hypothesis, we alternately applied the DNFB and DfE to the back skin of BALB/c mice for 8 weeks. Changes in mice skin lesions and the frequency of scratching behavior were recorded. The variation of Th1-related cytokines (interferon-γ [IFN-γ] and interleukin two [IL-2]) and Th2-related cytokines (IL-4 and IL-13) was detected in serum and lesional skin. Eventually, the BALB/c mice developed severe erythema, erosion, scarring, and excoriation on the entire back, showing a high frequency of scratching behavior. In addition, Th2 cells' dominant cytokines appeared in both serum and lesional skin. Those results indicate that alternating epicutaneous exposure to DNFB and DfE can produce AD-like models with typical clinical features and Th2-type immune responses in BALB/c mice. This model could be valuable for studying the pathogenesis of AD and developing novel therapeutic agents for it.

Atopic dermatitis (AD) is a common inflammatory skin disease, but current treatments for AD are mostly limited to the alleviation of symptoms and inhibition of inflammation. Allergen‐specific immunotherapy (ASIT) is the only curative approach for allergic diseases and could be a promising way to cure AD. Although ASIT has been gradually applied to patients with AD, there are still few studies on its efficacy evaluation and mechanisms. Based on our previous established AD mouse model by dinitrofluorobenzene and an extract of Dermatophagoides farina, we performed ASIT on this AD model through subcutaneous injection of Dermatophagoides farina extracts to evaluate the efficacy of ASIT and study its underlying mechanisms. Our results showed that ASIT could not only alleviate skin lesions and scratching behaviors of AD mice but also inhibit their Th2‐type immune responses. Furthermore, ASIT could increase the infiltration of monocyte‐derived dendritic cells in skin lesions but attenuated their maturation and production of interleukin 1α and interleukin 12/23 p40. As immature and semi‐mature dendritic cells preferentially induce tolerance, accumulation but inhibition of maturation of monocyte‐derived dendritic cells after ASIT may indicate a novel mechanism of ASIT and a potential therapeutic target for AD.

BackgroundAtopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease characterized by severe pruritus and eczematous lesions. Heterogeneity of AD has been reported among different racial groups according to clinical, molecular and genetic differences.ObjectiveThis study aimed to conduct an in‐depth transcriptome analysis of AD in Chinese population.MethodsWe performed single‐cell RNA sequencing (scRNA‐seq) analysis of skin biopsies from five Chinese adult patients with chronic AD and from four healthy controls, combined with multiplexed immunohistochemical analysis in whole‐tissue skin biopsies. We explored the functions of IL19 in vitro.ResultsScRNA‐seq analysis was able to profile a total of 87,853 cells, with keratinocytes (KCs) in AD manifesting highly expressed keratinocyte activation and pro‐inflammatory genes. KCs demonstrated a novel IL19+IGFL1+ subpopulation that increased in AD lesions. Inflammatory cytokines IFNG, IL13, IL26 and IL22 were highly expressed in AD lesions. In vitro, IL19 directly downregulated KRT10 and LOR in HaCaT cells and activated HaCaT cells to produce TSLP.ConclusionAbnormal proliferation and differentiation of keratinocytes contribute immensely to the pathogenesis of AD, whereas AD chronic lesions have witnessed significant presence of IL19+IGFL1+KCs, which may be involved in the disruption of the skin barrier, the connection and magnification of Th2 and Th17 inflammatory responses, and mediation of skin pruritus. Furthermore, progressive activation of multiple immune axes dominated by Type 2 inflammatory reaction occur in AD chronic lesions.