Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze.

Autor: Coenen I; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia., de Jong E; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia., Jones AC; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia., Khoo SK; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia., Foo S; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore., Howland SW; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore., Ginhoux F; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore., Le Souëf PN; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia., Holt PG; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia., Strickland DH; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia., Laing IA; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia., Leffler J; Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia. Electronic address: Jonatan.Leffler@telethonkids.org.au.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2024 Apr; Vol. 153 (4), pp. 1083-1094. Date of Electronic Publication: 2023 Dec 16.
DOI: 10.1016/j.jaci.2023.11.920
Abstrakt: Background: Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity as critical producers of type I interferons. pDCs also express the high-affinity IgE receptor through which type I interferon production may be negatively regulated. Whether antiviral function of pDCs is associated with recurrent episodes of wheeze in young children is not well understood.
Objective: We sought to evaluate the phenotype and function of circulating pDCs in children with a longitudinally defined wheezing phenotype.
Methods: We performed multiparameter flow cytometry on PBMCs from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDCs from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database.
Results: We observed a significant depletion of circulating pDCs in young children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the FcεRI on their pDCs. Based on transcriptomic analysis, pDCs from these individuals did not mount a robust systemic antiviral response as observed in children who displayed a nonrecurrent wheezing phenotype.
Conclusions: Our data suggest that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of high-affinity IgE receptor is increased and their function as major interferon producers is impaired during acute exacerbations of wheeze.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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