Li Xu, Li Zizhuo, Tang Mindan, Zhang Kaoyuan, Yang Ting, Zhong Weilong, Yu Bo, Wang Fang, Dou Xia
Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, China.
Institute of Dermatology, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
Front Immunol. 2025 May 15;16:1573130. doi: 10.3389/fimmu.2025.1573130. eCollection 2025.
Atopic dermatitis (AD), a prevalent inflammatory skin disease affecting 10%-20% of the population, is linked to the development of asthma through atopic march (AM). This study aims to explore the role of basophils in OVA-induced lung inflammation in the presence of AD-like skin lesions and investigate the potential contribution of thymic stromal lymphopoietin (TSLP) in activating basophils.
Mouse AM models were established in C57BL/6 mice using MC903 and OVA epicutaneous sensitization, followed by intranasal OVA challenges. An intraperitoneal OVA-sensitized asthma model was employed as the control group. RNA-Seq analysis was conducted on lung CD45 immune cells from these models. Histologic examinations, flow cytometry, and ELISA were used to examine the lung and systemic inflammatory response. Basophil depletion was achieved through intraperitoneal administration of anti-FcϵRIα mAb. The role of TSLP was investigated using TSLPR knockout mice.
As in the intraperitoneal sensitization model, AM model also induced eosinophilic lung inflammation in mice, resembling the AM process. The RNA-Seq analysis revealed differential gene expression, with genes related to basophils being prominent in AM model. Increased basophil activation and IL-4 production were observed in OVA epicutaneously sensitized mice. Basophil depletion attenuated the eosinophilic lung inflammation. TSLP levels increased with topical MC903, and TSLPR knockout reduced lung inflammation, suggesting TSLP is involved in basophil activation.
Basophils play a crucial role in OVA-induced lung inflammation in the context of AD-like skin lesions, and TSLP appears to drive basophil activation. Understanding these interactions provides insights for potential therapeutic interventions in AM-associated conditions.
特应性皮炎（AD）是一种常见的炎症性皮肤病，影响着10%-20%的人群，通过特应性进程（AM）与哮喘的发生相关。本研究旨在探讨在存在类AD皮肤病变的情况下嗜碱性粒细胞在卵清蛋白（OVA）诱导的肺部炎症中的作用，并研究胸腺基质淋巴细胞生成素（TSLP）在激活嗜碱性粒细胞中的潜在作用。
使用MC903和OVA经皮致敏在C57BL/6小鼠中建立小鼠AM模型，随后进行鼻内OVA激发。将腹腔注射OVA致敏的哮喘模型作为对照组。对这些模型的肺CD45免疫细胞进行RNA测序分析。采用组织学检查、流式细胞术和酶联免疫吸附测定（ELISA）来检测肺部和全身炎症反应。通过腹腔注射抗FcϵRIα单克隆抗体实现嗜碱性粒细胞耗竭。使用TSLPR基因敲除小鼠研究TSLP的作用。
与腹腔致敏模型一样，AM模型也在小鼠中诱导了嗜酸性肺部炎症，类似于AM进程。RNA测序分析显示基因表达存在差异，与嗜碱性粒细胞相关的基因在AM模型中尤为突出。在经皮OVA致敏的小鼠中观察到嗜碱性粒细胞活化增加和白细胞介素-4产生增加。嗜碱性粒细胞耗竭减轻了嗜酸性肺部炎症。局部使用MC903后TSLP水平升高，TSLPR基因敲除减轻了肺部炎症，表明TSLP参与嗜碱性粒细胞活化。
在类AD皮肤病变的背景下，嗜碱性粒细胞在OVA诱导的肺部炎症中起关键作用，并且TSLP似乎驱动嗜碱性粒细胞活化。了解这些相互作用为AM相关病症的潜在治疗干预提供了见解。
