新型屋尘螨过敏原derp39通过诱导皮肤屏障功能障碍加重小鼠特应性皮炎样炎症

IF 3.9 2区医学 Q2 ALLERGY

World Allergy Organization Journal Pub Date : 2025-03-01 DOI:10.1016/j.waojou.2025.101036

Shan Liu BSc , Ze-Lang Cai MS , Jingcheng Liu , Si-Yi Que BSc , Wan-Zhen Hu MS , Liang Chen MS , Jia-Jie Chen PhD , Kunmei Ji PhD

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引用次数: 0

摘要

室内尘螨（HDM）过敏原可诱发或加重过敏性炎症，包括特应性皮炎（AD）。破坏上皮屏障的物质可引发或加重阿尔茨海默病。新型HDM过敏原derp39诱导过敏性炎症的机制尚不清楚。我们的目的是研究Der p39对ad样炎症的影响及其相关机制。方法采用二硝基氯苯（DNCB）和Der p39建立AD模型小鼠。通过生理和形态学检查评估炎症严重程度。在HaCaT细胞（人表皮角质形成细胞）中检测了Der p39对炎症细胞因子释放和皮肤屏障蛋白表达的影响。western blots检测丝裂原活化蛋白激酶（MAPK）的活化情况。使用MAPK抑制剂来评估MAPK参与聚丝蛋白表达。结果1% DNCB预处理小鼠耳后，der p 39加重了变应性炎症（组织厚度）。与对照组相比，derp39致敏组织显示表皮和真皮增厚，炎症病变中肥大细胞和嗜酸性粒细胞数量增加。在HaCaT细胞中，derp39增加促炎白介素（il）的转录和产生，下调皮肤屏障蛋白聚丝蛋白和loricrin的表达，上调ERK、JNK和p38的磷酸化。抑制MAPK信号可挽救Der p 39处理细胞中的聚丝蛋白表达。结论HDM变应原derp39可增强变应性炎症，促进MAPK通路介导的表皮屏障功能障碍，提示derp39可能具有致病性和临床相关的免疫调节潜力。

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The novel house dust mite allergen Der p 39 exacerbates atopic dermatitis-like inflammation in mice by inducing skin barrier dysfunction

Background

House dust mite (HDM) allergens can induce or exacerbate allergic inflammation, including atopic dermatitis (AD). Substances that damage the epithelial barrier can trigger or worsen AD. The mechanism by which the novel HDM allergen Der p 39 induces allergic inflammation remains unclear. Our aim was to investigate the effects of Der p 39 on AD-like inflammation and associated mechanisms.

Methods

Dinitrochlorobenzene (DNCB) and Der p 39 were utilized to establish AD model mice. Inflammation severity was evaluated with physiological and morphological assays. The effects of Der p 39 on inflammatory cytokine release and skin barrier protein expression were examined in HaCaT cells (human epidermal keratinocytes). Mitogen-activated protein kinase (MAPK) activation was examined by western blots. MAPK inhibitors were employed to assess MAPK involvement in filaggrin expression.

Results

Der p 39 worsened allergic inflammation (tissue thickness) in murine ears pretreated with 1% DNCB. Compared to controls, Der p 39-sensitized tissues showed epidermal and dermal thickening with elevated numbers of mast cells and eosinophils in inflammatory lesions. Der p 39 increased transcription and production of pro-inflammatory interleukins (ILs), down-regulated expression of the skin barrier proteins filaggrin and loricrin, and upregulated phosphorylation of ERK, JNK and p38 in HaCaT cells. Inhibition of MAPK signaling rescued filaggrin expression in Der p 39-treated cells.

Conclusions

The HDM allergen Der p 39 enhances allergic inflammation and promotes MAPK pathway-mediated epidermal barrier dysfunction, suggesting that Der p 39 may possess pathogenic and clinically relevant immunomodulatory potential.

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来源期刊

World Allergy Organization Journal Immunology and Microbiology-Immunology

CiteScore

9.10

自引率

5.90%

发文量

审稿时长

9 weeks

期刊介绍： The official pubication of the World Allergy Organization, the World Allergy Organization Journal (WAOjournal) publishes original mechanistic, translational, and clinical research on the topics of allergy, asthma, anaphylaxis, and clincial immunology, as well as reviews, guidelines, and position papers that contribute to the improvement of patient care. WAOjournal publishes research on the growth of allergy prevalence within the scope of single countries, country comparisons, and practical global issues and regulations, or threats to the allergy specialty. The Journal invites the submissions of all authors interested in publishing on current global problems in allergy, asthma, anaphylaxis, and immunology. Of particular interest are the immunological consequences of climate change and the subsequent systematic transformations in food habits and their consequences for the allergy/immunology discipline.