摘要
背景：过敏致敏和对病毒感染的反应能力降低可能导致幼儿出现病毒引起的喘息和哮喘。浆细胞样树突状细胞（pDC）是一种罕见的免疫细胞，能产生I型干扰素（IFN-I），在协调针对病毒的免疫反应中起着关键作用。
目的：进一步探讨pDC在儿童哮喘中的作用。
方法：本研究基于7岁早期生命肺功能（ELLF）队列中71名儿童的子集。作为ELLF研究的一部分，参与者被描述为特应性致敏、病毒感染史和肺功能测试。在存在或不存在抗IgE的情况下，使用体外试验评估pDC对TLR7/8激动剂的反应。利用流式细胞术、多重细胞因子测定和分离的pDC的转录分析来评估反应。
结果：pDC反应在个体之间差异很大，与仅用TNF反应的人相比，在刺激后用IFN-I反应的人患哮喘的比例较低。仅TNF反应与特应性增加和IFN相关基因上调减少有关。抗IgE刺激降低了pDC的活化，这种降低与IgE受体（FcεR1）的基线表达有关。还观察到围绕TPM2、LILRA4和CLEC4C等基因的基因模块减少。
结论：这些发现共同表明，pDC反应是可变的，与哮喘有关，并且似乎受到环境刺激的影响。因此，这种反应似乎是儿童哮喘病理学的一个重要方面。
Reduced Type-I Interferon by Plasmacytoid Dendritic Cells and Asthma in School-Aged Children
Isabelle Coenen, Anya C Jones, Alice A White, Mari Takashima, Wen Ray Lee, Matthew D Wong, Dwan Vilcins, Ulrich Kadolsky, Ali Sadiq Cheema, Alka Saxena, Anthony Bosco, Keith Grimwood, Peter D Sly, Deborah H Strickland, Jonatan Leffler
Abstract
Background: Allergic sensitization and reduced ability to respond to viral infections may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDC) are rare immune cells that produce type I interferons (IFN-I) and play a key role in orchestrating immune responses against viruses.
Objective: To further evaluate the function of pDC in children with asthma.
Methods: This study was based on a subset of 71 children from the Early Life Lung Function (ELLF) cohort at the age of 7 years. As part of the ELLF study, participants were characterized for atopic sensitization, viral infection history, and lung function testing. pDC responses to a TLR7/8 agonist were assessed in the presence or absence of anti-IgE using an in vitro assay. Responses were evaluated utilizing flow cytometry, multiplexed cytokine assays, and transcriptional analysis of isolated pDC.
Results: pDC responses varied considerably across individuals, and those who responded with IFN-I following stimulation showed a lower proportion of asthma compared to those who responded with TNF-only. A TNF-only response was associated with increased atopy and reduced upregulation of IFN-associated genes. Anti-IgE stimulation reduced pDC activation, and the reduction was associated with baseline expression of the IgE receptor (FcεR1). A reduction in a gene module centralized around genes such as TPM2, LILRA4, and CLEC4C was also observed.
Conclusion: Together, these findings suggest that pDC responses are variable, associated with asthma, and appear influenced by environmental stimuli. This response thus appears to be an important aspect of asthma pathology in children.
背景：过敏致敏和对病毒感染的反应能力降低可能导致幼儿出现病毒引起的喘息和哮喘。浆细胞样树突状细胞（pDC）是一种罕见的免疫细胞，能产生I型干扰素（IFN-I），在协调针对病毒的免疫反应中起着关键作用。
目的：进一步探讨pDC在儿童哮喘中的作用。
方法：本研究基于7岁早期生命肺功能（ELLF）队列中71名儿童的子集。作为ELLF研究的一部分，参与者被描述为特应性致敏、病毒感染史和肺功能测试。在存在或不存在抗IgE的情况下，使用体外试验评估pDC对TLR7/8激动剂的反应。利用流式细胞术、多重细胞因子测定和分离的pDC的转录分析来评估反应。
结果：pDC反应在个体之间差异很大，与仅用TNF反应的人相比，在刺激后用IFN-I反应的人患哮喘的比例较低。仅TNF反应与特应性增加和IFN相关基因上调减少有关。抗IgE刺激降低了pDC的活化，这种降低与IgE受体（FcεR1）的基线表达有关。还观察到围绕TPM2、LILRA4和CLEC4C等基因的基因模块减少。
结论：这些发现共同表明，pDC反应是可变的，与哮喘有关，并且似乎受到环境刺激的影响。因此，这种反应似乎是儿童哮喘病理学的一个重要方面。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Allergy. 2025 Aug 13. doi: 10.1111/all.70005.）
Reduced Type-I Interferon by Plasmacytoid Dendritic Cells and Asthma in School-Aged Children
Isabelle Coenen, Anya C Jones, Alice A White, Mari Takashima, Wen Ray Lee, Matthew D Wong, Dwan Vilcins, Ulrich Kadolsky, Ali Sadiq Cheema, Alka Saxena, Anthony Bosco, Keith Grimwood, Peter D Sly, Deborah H Strickland, Jonatan Leffler
Abstract
Background: Allergic sensitization and reduced ability to respond to viral infections may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDC) are rare immune cells that produce type I interferons (IFN-I) and play a key role in orchestrating immune responses against viruses.
Objective: To further evaluate the function of pDC in children with asthma.
Methods: This study was based on a subset of 71 children from the Early Life Lung Function (ELLF) cohort at the age of 7 years. As part of the ELLF study, participants were characterized for atopic sensitization, viral infection history, and lung function testing. pDC responses to a TLR7/8 agonist were assessed in the presence or absence of anti-IgE using an in vitro assay. Responses were evaluated utilizing flow cytometry, multiplexed cytokine assays, and transcriptional analysis of isolated pDC.
Results: pDC responses varied considerably across individuals, and those who responded with IFN-I following stimulation showed a lower proportion of asthma compared to those who responded with TNF-only. A TNF-only response was associated with increased atopy and reduced upregulation of IFN-associated genes. Anti-IgE stimulation reduced pDC activation, and the reduction was associated with baseline expression of the IgE receptor (FcεR1). A reduction in a gene module centralized around genes such as TPM2, LILRA4, and CLEC4C was also observed.
Conclusion: Together, these findings suggest that pDC responses are variable, associated with asthma, and appear influenced by environmental stimuli. This response thus appears to be an important aspect of asthma pathology in children.
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