Evidence map›Paper›PMID 40245497›Full record

ArticleEBioMedicine2025

An unconventional T cell nexus drives HCK-mediated chronic obstructive pulmonary disease in mice.

Amy T Hsu, Robert J J O'Donoghue, Evelyn Tsantikos, Timothy A Gottschalk, Jessica G Borger, Nicholas A Gherardin, Calvin Xu, Hui-Fern Koay, Dale I Godfrey, Matthias Ernst and 2 more

Abstract read
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In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Amy T HsuDepartment of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, 3004, Australia.
Robert J J O'DonoghueOlivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, Victoria, 3084, Australia.
Evelyn TsantikosDepartment of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, 3004, Australia.
Timothy A GottschalkDepartment of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, 3004, Australia.
Jessica G BorgerDepartment of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, 3004, Australia.
Nicholas A GherardinDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Calvin XuDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Hui-Fern KoayDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Dale I GodfreyDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Matthias ErnstOlivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, Victoria, 3084, Australia.
Gary P AndersonLung Health Research Centre, Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Margaret L HibbsDepartment of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, 3004, Australia. Electronic address: Margaret.Hibbs@monash.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease leading to progressive, destructive lung function decline, disability and death, and it is refractory to all current treatments. Haematopoietic cell kinase (HCK) is a druggable SRC-family non-receptor protein tyrosine kinase and COPD candidate gene. It is implicated in the chronic and non-resolving inflammation that causes mucosecretory bronchitis and destruction of small airways and alveoli, but how it drives pathophysiology remains obscure.

methodsStudies primarily utilised gene-targeted mice with a gain-of-function mutation in Hck that rendered the enzyme constitutively active. Bone marrow chimeras were established to determine the origin of disease, and the lung disease was investigated using histopathology, morphometry, flow cytometry and single-cell sequencing techniques. Detailed pathways mediating disease pathogenesis were examined using specialised knockout mice.

findingsHck

interpretationThese findings highlight the role of HCK as an apical regulator of an unconventional T cell axis that drives IL-17A/G-CSF/granulocyte-mediated pathology in COPD, and underscore the rationale for therapeutically targeting HCK.

fundingThis work received support from the National Health and Medical Research Council Australia, the Victorian Cancer Agency, Melbourne Australia, the Australian Research Council, the Australian Government and the School of Translational Medicine, Monash University, Australia.

Indexed as

Proto-Oncogene Proteins c-hckPulmonary Disease, Chronic ObstructiveT-LymphocytesAnimalsDisease Models, AnimalGranulocyte Colony-Stimulating FactorInterleukin-17LungMiceMice, KnockoutGranulocyte Colony-Stimulating FactorInterleukin-17Proto-Oncogene Proteins c-hckChronic obstructive pulmonary diseaseConstitutive HCK activationGranulocytesIL-17A/G-CSF axisMucus-producing goblet cellsUnconventional T cells

Identifiers

PMID40245497
PMCPMC12143211

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.