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Cited by 15Asthma and respiratory diseasesOccupational exposure and asthmaAllergic Rhinitis and Sensitization

Manipulation of dipeptidylpeptidase 10 in mouse and human in vivo and in vitro models indicates a protective role in asthma

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Zhang, Youming, Poobalasingam, Thanushiyan, Yates, Laura L., Walker, Simone A., Taylor, Martin S., Chessum, Lauren, Harrison, Jackie, Tsaprouni, Loukia +5 more·2018·Disease Models & Mechanisms
DOI 10.1242/dmm.031369PMC PMC5818078
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Abstract

We previously identified dipeptidylpeptidase 10 (DPP10) on chromosome 2 as a human asthma susceptibility gene, through positional cloning. Initial association results were confirmed in many subsequent association studies but the functional role of DPP10 in asthma remains unclear. Using the MRC Harwell N-ethyl-N-nitrosourea (ENU) DNA archive, we identified a point mutation in Dpp10 that caused an amino acid change from valine to aspartic acid in the β-propeller region of the protein. Mice carrying this point mutation were recovered and a congenic line was established (Dpp10145D). Macroscopic examination and lung histology revealed no significant differences between wild-type and Dpp10145D/145D mice. However, after house dust mite (HDM) treatment, Dpp10 mutant mice showed significantly increased airway resistance in response to 100 mg/ml methacholine. Total serum IgE levels and bronchoalveolar lavage (BAL) eosinophil counts were significantly higher in homozygotes than in control mice after HDM treatment. DPP10 protein is present in airway epithelial cells and altered expression is observed in both tissue from asthmatic patients and in mice following HDM challenge. Moreover, knockdown of DPP10 in human airway epithelial cells results in altered cytokine responses. These results show that a Dpp10 point mutation leads to increased airway responsiveness following allergen challenge and provide biological evidence to support previous findings from human genetic studies. This article has an associated First Person interview with the first author of the paper.

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  • This astrocyte subcluster was enriched for genes involved in extracellular matrix organization, metabolic support, and inflammatory modulation.

    “This subcluster was enriched for genes involved in extracellular matrix organization [102, 135, 136], metabolic support [135, 137], and inflammatory modulation [138–141].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [138]

    The Results section ('DPP10 protein is present in human asthmatic airway epithelial cells and modulation of DPP10 affects key inflammatory mediators'; page unavailable) reports that changing DPP10 expression affects inflammatory-mediator release in airway epithelial cells. It does not examine an astrocyte subcluster or show enrichment of genes involved in inflammatory modulation; the cited paper therefore supports only the broader inflammatory-modulation aspect, in a different cell type. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
Zhang, Y., Poobalasingam, T., Yates, L. L., Walker, S. A., Taylor, M. S., Chessum, L., Harrison, J., Tsaprouni, L., Adcock, I. M., Lloyd, C. M., Cookson, W. O., Moffatt, M. F., & Dean, C. H.
Affiliations
  • Imperial College London (GB)
  • Centre for Human Genetics (GB)
  • Mary Lyon Centre at MRC Harwell (GB)
Corresponding author
  • Zhang, Youming
  • Dean, Charlotte H.
ORCID
Venue
Disease Models & Mechanisms
Publisher
The Company of Biologists
Published
2018-01-01
Volume
11
Issue
1
ISSN
  • 1754-8403 (ISSN-L)
  • 1754-8411
DOI
10.1242/dmm.031369
PMC
PMC5818078
OpenAlex
W2781201093
Cited by
15
References
2
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1
FWCI
0.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Disease Models & Mechanisms (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • HighWire Press Open Archive (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (WT 077959, WT096964)
  • Medical Research Council
  • National Heart and Lung Institute
  • Research Councils UK
  • MRC Harwell
  • Innovative Medicines Initiative
Topics
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
Keywords
DPP10, asthma, asthma susceptibility genes, positional cloning, ENU mutagenesis, congenic mice, airway hyperresponsiveness, methacholine responsiveness, serum IgE, eosinophils, airway epithelial cells, cytokine response
MeSH terms
Amino Acid Sequence, Animals, Asthma, Base Sequence, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Disease Models, Animal, Epithelial Cells, Ethylnitrosourea, Genotype, Homozygote, Humans, Hypersensitivity, Inflammation, Lung, Mice, Mutant Strains, Mutation, Reproducibility of Results, Inflammation Mediators, Pyroglyphidae, Mice

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