TNFα counters skin inflammation by restraining mast cell-dependent TSLP production.

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology Pub Date : 2025-04-04 DOI:10.1016/j.jaci.2025.03.019

Davender Redhu, Vandana Kumari, Kristin Franke, Karin Hartmann, Margitta Worm, Magda Babina

{"title":"TNFα counters skin inflammation by restraining mast cell-dependent TSLP production.","authors":"Davender Redhu, Vandana Kumari, Kristin Franke, Karin Hartmann, Margitta Worm, Magda Babina","doi":"10.1016/j.jaci.2025.03.019","DOIUrl":null,"url":null,"abstract":"Background: TNFα is an important proinflammatory cytokine, but its neutralization in the management of inflammatory skin disorders like psoriasis may trigger eczematous skin lesions as an adverse reaction.Objectives: This study aimed to elucidate whether TNF-α may protect from skin inflammation and to identify in detail the underlying mechanisms.Methods: Wildtype, TNF-α-deficient, TSLPR-deficient, mast cell (MC)-deficient, TNF-α-TSLPR-double-deficient and TNF-α-MC-double-deficient mice were subjected to a skin inflammation model and inspected by physical, clinical, histological, immunohistochemical and bioanalytical techniques.Results: TNFα deficiency promoted skin inflammation. This was accompanied by MC hyperplasia and potent TSLP production in lesional skin and serum of TNFα deficient mice. Specifically, MCs were found to be responsible for inducing high levels of TSLP in the epidermis, compromising barrier function and initiating inflammation. In contrast, the production of immunoglobulins, including IgE, was reduced in mice lacking TNFα.Conclusions: TNFα restrains MC-dependent TSLP production and the onset of eczema.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4000,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jaci.2025.03.019","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: TNFα is an important proinflammatory cytokine, but its neutralization in the management of inflammatory skin disorders like psoriasis may trigger eczematous skin lesions as an adverse reaction.

Objectives: This study aimed to elucidate whether TNF-α may protect from skin inflammation and to identify in detail the underlying mechanisms.

Methods: Wildtype, TNF-α-deficient, TSLPR-deficient, mast cell (MC)-deficient, TNF-α-TSLPR-double-deficient and TNF-α-MC-double-deficient mice were subjected to a skin inflammation model and inspected by physical, clinical, histological, immunohistochemical and bioanalytical techniques.

Results: TNFα deficiency promoted skin inflammation. This was accompanied by MC hyperplasia and potent TSLP production in lesional skin and serum of TNFα deficient mice. Specifically, MCs were found to be responsible for inducing high levels of TSLP in the epidermis, compromising barrier function and initiating inflammation. In contrast, the production of immunoglobulins, including IgE, was reduced in mice lacking TNFα.

Conclusions: TNFα restrains MC-dependent TSLP production and the onset of eczema.

查看原文本刊更多论文

TNFα通过抑制肥大细胞依赖性TSLP的产生来对抗皮肤炎症。

背景：TNFα是一种重要的促炎细胞因子，但在治疗炎性皮肤疾病如牛皮癣时，其中和可能引发湿疹性皮肤病变作为不良反应。目的：本研究旨在阐明TNF-α是否可以预防皮肤炎症，并详细确定其潜在机制。方法：建立野生型、TNF-α-缺陷型、tslpr缺陷型、肥大细胞（MC）缺陷型、TNF-α- tslpr双缺陷型和TNF-α-MC双缺陷型小鼠皮肤炎症模型，采用物理、临床、组织学、免疫组织化学和生物分析技术进行检测。结果：TNFα缺乏促进皮肤炎症反应。在TNFα缺乏小鼠的病变皮肤和血清中，伴有MC增生和强效TSLP的产生。具体来说，MCs被发现负责在表皮中诱导高水平的TSLP，损害屏障功能并引发炎症。相反，在缺乏TNFα的小鼠中，免疫球蛋白（包括IgE）的产生减少。结论：TNFα抑制mc依赖性TSLP的产生和湿疹的发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Allergy and Clinical Immunology 医学-过敏

CiteScore

25.90

自引率

7.70%

发文量

1302

审稿时长

38 days

期刊介绍： The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.