Deep identifiable modeling of single-cell atlases enables zero-shot query of cellular states DOI Creative Commons
Mingze Dong, Kriti Agrawal, Rong Fan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 15, 2023

How to identify true biological differences across samples while overcoming batch effects has been a persistent challenge in single-cell RNA-seq data analysis, hindering analyses datasets for transferable findings. In this work, we show that scaling up deep identifiable models leads surprisingly effective solution challenging task. We developed scShift, variational inference framework with theoretical support disentangling batch-dependent and independent variations. By training the model compendiums of scRNA-seq atlases, scShift shows remarkable zero-shot capabilities revealing representations cell types states effects. employed systematically compare lung fibrosis different datasets, tissues experimental systems. uniquely extrapolates previously unseen post-COVID-19 fibrosis, characterizing universal myeloid-fibrosis signatures, potential repurposing drug targets fibrosis-associated interactions. Evaluations over 200 trained demonstrate emergent law beyond transition threshold, respect dataset diversity. With its performance on massive exceptional capabilities, represents an important advance toward next-generation computational analysis.

Language: Английский

Monocytes and macrophages: emerging mechanisms and novel therapeutic targets in pulmonary fibrosis DOI Creative Commons
C.Y. Perrot, Τheodoros Karampitsakos, José D. Herazo-Maya

et al.

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 325(4), P. C1046 - C1057

Published: Sept. 11, 2023

Pulmonary fibrosis results from a plethora of abnormal pathogenetic events. In idiopathic pulmonary (IPF), inhalational, environmental, or occupational exposures in genetically and epigenetically predisposed individuals trigger recurrent cycles alveolar epithelial cell injury, activation coagulation pathways, chemoattraction, differentiation monocytes into monocyte-derived macrophages (Mo-AMs). When these events happen intermittently repeatedly throughout the individual's life cycle, wound repair process becomes aberrant leading to bronchiolization distal air spaces, fibroblast accumulation, extracellular matrix deposition, loss alveolar-capillary architecture. The role immune dysregulation IPF pathogenesis progression has been underscored past mainly after disappointing immunosuppressant use patients; however, recent reports highlighting prognostic mechanistic roles Mo-AMs revived interest IPF. this review, we will discuss cells onset IPF, as well potential targeted therapies.

Language: Английский

Citations

37
Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine DOI
Ayodeji Adegunsoye, Jonathan A. Kropski, Jürgen Behr

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 210(4), P. 401 - 423

Published: April 4, 2024

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) other progressive fibrotic interstitial lung diseases (ILDs), emphasizing contribution heritable factors. This state-of-the-art review synthesizes evidence on significant contributors to (PF), including rare variants common single nucleotide polymorphisms (SNPs). The MUC5B promoter variant is unusual, a SNP that markedly elevates risk early established PF. We address utility variation in enhancing understanding disease pathogenesis, clinical phenotypes, improving definitions, informing prognosis treatment response. Critical research gaps are highlighted, particularly underrepresentation non-European ancestries PF studies exploration phenotypes beyond usual pneumonia (UIP)/IPF. discuss role telomere length, often critically short PF, its link progression mortality, underscoring complexity involving biology genes (TERT, TERC) others like SFTPC MUC5B. Additionally, we potential gene-by-environment interactions modulate manifestation, advocating for precision medicine Insights from gene expression profiling multi-omic analyses highlight promise pathogenesis offer new approaches care, therapeutic drug development, biomarker discovery. Finally, ethical, legal, social implications therapies stressing need sound practices informed discussions. Looking forward, advocate comprehensive testing panels polygenic scores improve management related ILDs across diverse populations.

Language: Английский

Citations

11
The lung microbiome in interstitial lung disease DOI Open Access

Sheridan G Mikhail,

David N. O’Dwyer

Breathe, Journal Year: 2025, Volume and Issue: 21(2), P. 240167 - 240167

Published: April 1, 2025

Interstitial lung disease (ILD) is a heterogeneous chronic form of disease. The pathogenesis ILD poorly understood and common ILD, idiopathic pulmonary fibrosis (IPF) associated with poor prognosis. There evidence for substantial dysregulated immune responses in ILD. microbiome key regulator the response, correlates alveolar immunity clinical outcomes Most observational studies have been conducted patients IPF. A consistent observation these that bacterial burden elevated IPF predicts mortality. However, our understanding mechanism incomplete role other forms limited. microbiomes oropharynx gut may implications but require further research. Here, we discuss supporting IPF, briefly describe putative oral–lung axis gut–lung

Language: Английский

Citations

1
Mast-cell expressed membrane protein-1 is expressed in classical monocytes and alveolar macrophages in idiopathic pulmonary fibrosis and regulates cell chemotaxis, adhesion, and migration in a TGFβ-dependent manner DOI
C.Y. Perrot, Τheodoros Karampitsakos, Avraham Unterman

et al.

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(3), P. C964 - C977

Published: Jan. 8, 2024

MCEMP1 is highly expressed in circulating classical monocytes and alveolar macrophages IPF, regulated by TGFβ, participates the chemotaxis, adhesion, migration of modulating effect TGFβ RHO activity.

Language: Английский

Citations

8
Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis DOI
Amy Zhao, Avraham Unterman, Nebal Abu Hussein

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 210(10), P. 1252 - 1266

Published: June 26, 2024

Fibrotic hypersensitivity pneumonitis (FHP) is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms.

Language: Английский

Citations

8
Peripheral blood monocyte count and outcomes in patients with interstitial lung disease: a systematic review and meta-analysis DOI Creative Commons
Bohyung Min, Amanda Grant-Orser, Kerri A. Johannson

et al.

European Respiratory Review, Journal Year: 2023, Volume and Issue: 32(169), P. 230072 - 230072

Published: Sept. 6, 2023

Peripheral blood monocyte counts have been associated with poor outcomes in interstitial lung disease (ILD). However, studies are limited by variable biomarker thresholds, analytic approaches and heterogenous populations. This systematic review meta-analysis characterised the relationship between monocytes clinical ILD.

Language: Английский

Citations

11
The Relationship Between Differential Expression of Non-coding RNAs (TP53TG1, LINC00342, MALAT1, DNM3OS, miR-126-3p, miR-200a-3p, miR-18a-5p) and Protein-Coding Genes (PTEN, FOXO3) and Risk of Idiopathic Pulmonary Fibrosis DOI
G. F. Korytina, V. A. Markelov, Irshat A. Gibadullin

et al.

Biochemical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

Citations

0
Investigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis DOI
Paolo Spagnolo, Roberto Tonelli, Marco Mura

et al.

Expert Opinion on Investigational Drugs, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 20

Published: Feb. 7, 2025

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease of unknown cause that occurs primarily in older adults and associated with poor quality life substantial healthcare utilization. IPF has dismal prognosis. Indeed, first-line therapy, which includes nintedanib pirfenidone, does not stop progression often tolerability issues. Therefore, there remains high medical need for more efficacious better tolerated treatments. Gene therapy relatively unexplored field research the potential to mitigate range profibrotic pathways by introducing genetic material into cells. Here, we summarize critically discuss publications have explored safety efficacy gene experimentally-induced animals, as clinical studies humans been published yet. The application requires further investigation address several technical biological hurdles, improve vectors' design, drug delivery, target selection, off-target effects develop markers penetration Long-term data are needed bring one step closer practice.

Language: Английский

Citations

0
The Intersection between Immune System and Idiopathic Pulmonary Fibrosis—A Concise Review DOI
Hongli Liu,

Huachun Cui,

Gang Liu

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: 3(1), P. 10004 - 10004

Published: Jan. 1, 2025

Idiopathic pulmonary fibrosis (IPF) is marked by progressive alveolar destruction, impaired tissue regeneration, and relentless fibrogenesis, culminating in respiratory failure death. A diverse array of resident non-resident cells within the lung contribute to disease pathogenesis. Notably, immune cells, both recruited, respond cues from sites injury undergoing phenotypic transitions producing a wide range mediators that influence, initiate, or dictate function, dysfunction, key effector IPF pathology, such as epithelial fibroblasts, capillary endothelial cells. The role system has undergone an interesting evolution, oscillating initial enthusiasm skepticism, now renewed focus. This shift reflects past failures immune-targeting therapies for unprecedented insights into cell heterogeneity provided emerging technologies. In this article, we review historical evolution perspectives on system's pathogenesis examine lessons learned previous therapeutic targeting responses. We discuss major types implicated progression, highlighting their mechanisms action. Finally, identify knowledge gaps propose future directions research IPF.

Language: Английский

Citations

0
Interaction between nasal epithelial cells and Tregs in allergic rhinitis responses to allergen via CCL1/CCR8 DOI Creative Commons
Jichao Sha, Maolin Yang, Yingying Lei

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

The airway epithelial barrier is the first defence against aeroallergens. Nasal cells (NECs) are vital in regulating innate and adaptive mucosal immunity allergic rhinitis (AR). Tregs produce cytokines essential for immunomodulatory activities allergen immunotherapy. Understanding relationship between NECs hyperresponsiveness network developing novel treatments. Using an vitro human Treg-NEC co-culture system of AR health control group, chemokine expression profiles were examined using immunohistochemistry, RT-PCR, ELISA, functional surface markers detected flow cytometric analysis. Correlation analysis was performed derived from CD4+CD8+Foxp3+ group after co-culture, including TSLP/CTLA4, CCL1/CTLA4, TSLP/CCR8, CCL1/CCR8. CCR8 CTLA-4 expressions co-culturing higher than single culture. Following Derp1 stimulation, TSLP, IL-25 TGF-β + increased. CCL1 mRNA lower group. In TSLP higher, protein levels decreased. There no significant differences IL-25, IL-10. When Treg added, changes similar to that observed pNECs. After CCL1/CCR8 positively correlated AR. Human pNECs can communicate with directly, may be pathway play a key role immune

Language: Английский

Citations

0