ArticleJCI insight2021
Hedgehog interacting protein-expressing lung fibroblasts suppress lymphocytic inflammation in mice.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026Review
- HHIP's dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- New approaches to uncover COPD pathobiology and develop therapies.JCI insight · 2026Review
- A Single Cell Atlas of the COPD Lung Identifies Inflammatory Reprogramming in Fibroblasts.International journal of chronic obstructive pulmonary disease · 2026Article
- HHIP protein interactions in lung cells provide insight into COPD pathogenesis.Human molecular genetics · 2025Article
- The Microbiota and Evolution of Obesity.Endocrine reviews · 2025Review
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Mechanics-activated fibroblasts promote pulmonary group 2 innate lymphoid cell plasticity propelling silicosis progression.Nature communications · 2024Article
- Impact of HHIP gene polymorphisms on phenotypes, serum IL-17 and IL-18 in COPD patients of the Chinese Han population.Respiratory research · 2024Article
- Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells.EBioMedicine · 2024Article
- The Mechanism by Which Hedgehog Interacting Protein (HHIP) in Cancer-Associated Fibroblasts Regulate the Secretion of Inflammatory Factors Through the JAK1/STAT3 Pathway Affecting Prostate Cancer Stemness.Journal of inflammation research · 2024Article
- Bad Neighbors or Bad Neighborhoods: Pathogenic Residency of T Cells in Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2023Article
- Activation of CD8American journal of respiratory and critical care medicine · 2023Article
- Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside.The Journal of clinical investigation · 2023Review
- Twenty years of changes in the definition of early chronic obstructive pulmonary disease.Chinese medical journal pulmonary and critical care medicine · 2023Review
- Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts.Nucleic acids research · 2022Article
- Identification, discrimination and heterogeneity of fibroblasts.Nature communications · 2022Review
- Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder.The Lancet. Respiratory medicine · 2022Review
- Advances in acute COPD exacerbation: clarifying specific immune mechanisms of infectious and noninfectious factors.Therapeutic advances in respiratory diseaseReview
- Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking and characterized by chronic inflammation in vulnerable individuals. However, it is unknown how genetic factors may shape chronic inflammation in COPD. To understand how hedgehog interacting protein, encoded by HHIP gene identified in the genome-wide association study in COPD, plays a role in inflammation, we utilized Hhip+/- mice that present persistent inflammation and emphysema upon aging similar to that observed in human COPD. By performing single-cell RNA sequencing of the whole lung from mice at different ages, we found that Hhip+/- mice developed a cytotoxic immune response with a specific increase in killer cell lectin-like receptor G1-positive CD8+ T cells with upregulated Ifnγ expression recapitulating human COPD. Hhip expression was restricted to a lung fibroblast subpopulation that had increased interaction with CD8+ T lymphocytes in Hhip+/- compared with Hhip+/+ during aging. Hhip-expressing lung fibroblasts had upregulated IL-18 pathway genes in Hhip+/- lung fibroblasts, which was sufficient to drive increased levels of IFN-γ in CD8+ T cells ex vivo. Our finding provides insight into how a common genetic variation contributes to the amplified lymphocytic inflammation in COPD.
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Registered trials
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.