Asthma and Lower Airway Disease - Reduced Type-I Interferon by Plasmacytoid Dendritic Cells and Asthma in School-Aged Children

Sep 29, 2026

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Background: Allergic sensitization and diminished antiviral responsiveness may contribute to virus-induced wheeze and later asthma development. Plasmacytoid dendritic cells (pDC) are rare immune cells that generate type I interferons (IFN-I) and coordinate antiviral immunity. Objective: Evaluate pDC function in children with asthma. Methods: Analyze a subset of 71 7-year-old children from the ELLF cohort using in vitro TLR7/8 agonist stimulation ± anti-IgE, assessed by flow cytometry, cytokines, and pDC transcriptional profiling.

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Allergy ORIGINAL ARTICLE OPEN ACCESS Asthma and Lower Airway Disease Reduced Type-I Interferon by Plasmacytoid Dendritic Cells and Asthma in School-Aged Children Isabelle Coenen1 | Anya C. Jones1,2 | Alice A. White3 | Mari Takashima4 | Wen Ray Lee4 | Matthew D. Wong4 | Dwan Vilcins4 | Ulrich Kadolsky5 | Ali Sadiq Cheema5 | Alka Saxena5 | Anthony Bosco2,6,7 | Keith Grimwood8 | Peter D. Sly4 | Deborah H. Strickland1 | Jonatan Leffler1 1Wal-Yan Respiratory Research Centre, The Kids Research Institute Australia, University of Western Australia, Perth, Western Australia, Australia | 2INSiGENe Pty Ltd, Perth, Western Australia, Australia | 3The Kids Research Institute Australia, University of Western Australia, Perth, Western Australia, Australia | 4Child Health Research Centre, The University of Queensland, South Brisbane, Queensland, Australia | 5Genomics WA, Perth, Western Australia, Australia | 6Asthma and Airway Disease Research Center, University of Arizona, Tucson, Arizona, USA | 7Department of Immunobiology, University of Arizona College of Medicine, Tucson, Arizona, USA | 8School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia Correspondence: Jonatan Leffler ([jonatan.leffler@thekids.org.au](jonatan.leffler@thekids.org.au)) Received: 17 February 2025 | Revised: 11 June 2025 | Accepted: 29 June 2025 Funding: The study was funded by the Wal-yan Respiratory Research Centre, [and J.L. is](and J.L. is) supported by a fellowship from the Stan Perron Charitable Foundation. Keywords: childhood asthma | IgE | interferon response | plasmacytoid dendritic cells 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 7years. As part ofthe 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. 1 | Introduction In young children, wheezing during a viral respiratory infection is common and affects almost 50% of children before the age of 5 years [1] . However, some children experience recurrent episodes of wheeze, and a subset of these are subsequently diagnosed with asthma. Impaired innate immune responses to viruses [2], atopic sensitization [3] and repeated This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2025 Th

FAQs

Why are plasmacytoid dendritic cells (pDC) important in childhood asthma?

pDC are rare immune cells that produce type I interferons (IFN-I), which are central to antiviral responses. The document links altered pDC function with asthma development and pathology in children.

How did the study assess pDC responses in children?

The study used an in vitro assay with pDC stimulation by a TLR7/8 agonist, with and without anti-IgE. Responses were evaluated using flow cytometry, multiplex cytokine assays, and transcriptional analysis.

What was the main finding about IFN-I versus TNF-only pDC responses?

Individuals who showed an IFN-I response after stimulation had a lower proportion of asthma than those showing a TNF-only response. TNF-only responses were associated with increased atopy and reduced upregulation of IFN-associated genes.

Sep 29, 2026

Uploaded by dawugda