4.6 Article

Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models

Journal

PLOS ONE
Volume 16, Issue 6, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0250533

Keywords

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Funding

  1. TUBITAK [116Z272]
  2. Dokuz Eylul University [2016.KB.SAG.020, 2017.KB. SAG.029]
  3. European Molecular Biology Organization (EMBO) [3073]

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Asthma is a heterogeneous disease that can be classified into eosinophilic asthma and neutrophilic asthma. Eosinophilic asthma is treatment-responsive and associated with allergic asthma, while neutrophilic asthma is treatment-resistant. Understanding the differences between these endotypes is crucial for developing effective diagnosis and treatment strategies.
Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7(+) activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.

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