Roles of Mesenchymal Cells in the Lung: From Lung Development to Chronic Obstructive Pulmonary Disease

Nasri, Amina; Foisset, Florent; Ahmed, Engi; Lahmar, Zakaria Mohamed; Vachier, Isabelle; Jørgensen, Christian; Assou, Saïd; Bourdin, Arnaud; Vos, John De

doi:10.3390/cells10123467

Cited by 26 publications

(19 citation statements)

References 190 publications

(217 reference statements)

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“…It is essential to precisely determine the taxonomy of lung mesenchymal cells during asthma development by scRNA-seq. Many studies have identified an increased expression of the fibroblast protein (S100A4), matrix metalloproteinases (MMP2 and MMP9) released by myofibroblasts and Fibs can remodel the mesenchymal cells, which play crucial roles in airway fibrosis ( 55 ). Our data proved differential genes (MMP2, S100A2) in MC1, MC2 and MC4 exhibited distinct structural cell interactions in the asthmatic model.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic characterization reveals the landscape of airway remodeling and inflammation in a cynomolgus monkey model of asthma

Wang

Dong²,

Pan³

et al. 2022

Front. Immunol.

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Monkey disease models, which are comparable to humans in terms of genetic, anatomical, and physiological characteristics, are important for understanding disease mechanisms and evaluating the efficiency of biological treatments. Here, we established an A.suum-induced model of asthma in cynomolgus monkeys to profile airway inflammation and remodeling in the lungs by single-cell RNA sequencing (scRNA-seq). The asthma model results in airway hyperresponsiveness and remodeling, demonstrated by pulmonary function test and histological characterization. scRNA-seq reveals that the model elevates the numbers of stromal, epithelial and mesenchymal cells (MCs). Particularly, the model increases the numbers of endothelial cells (ECs), fibroblasts (Fibs) and smooth muscle cells (SMCs) in the lungs, with upregulated gene expression associated with cell functions enriched in cell migration and angiogenesis in ECs and Fibs, and VEGF-driven cell proliferation, apoptotic process and complement activation in SMCs. Interestingly, we discover a novel Fib subtype that mediates type I inflammation in the asthmatic lungs. Moreover, MCs in the asthmatic lungs are found to regulate airway remodeling and immunological responses, with elevated gene expression enriched in cell migration, proliferation, angiogenesis and innate immunological responses. Not only the numbers of epithelial cells in the asthmatic lungs change at the time of lung tissue collection, but also their gene expressions are significantly altered, with an enrichment in the biological processes of IL-17 signaling pathway and apoptosis in the majority of subtypes of epithelial cells. Moreover, the ubiquitin process and DNA repair are more prevalent in ciliated epithelial cells. Last, cell-to-cell interaction analysis reveals a complex network among stromal cells, MCs and macrophages that contribute to the development of asthma and airway remodeling. Our findings provide a critical resource for understanding the principle underlying airway remodeling and inflammation in a monkey model of asthma, as well as valuable hints for the future treatment of asthma, especially the airway remodeling-characterized refractory asthma.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic characterization reveals the landscape of airway remodeling and inflammation in a cynomolgus monkey model of asthma

Wang

Dong²,

Pan³

et al. 2022

Front. Immunol.

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“…However, the status of lung growth and development determines the susceptibility to COPD, which seems to have a close relationship with genetics. 9 , 10 We should focus on airway hyperreactivity, which is an independent predictor of COPD and can exist independently without asthma and bronchitis, suggesting that the inflammatory response in COPD is different from asthma. 6 , 11 In addition to the above causes, inflammatory mechanisms, oxidative stress, and protease-antiprotease imbalance are also involved in the development of COPD.…”

Section: Introductionmentioning

confidence: 99%

Pathological Mechanism and Targeted Drugs of COPD

Guo¹,

Li²,

Piao³

et al. 2022

COPD

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Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis, emphysema, and small airway obstruction. Incompletely reversible airflow limitation, inflammation, excessive mucus secretion and bronchial mucosal epithelial lesions are the main pathological basis of the disease. The prevalence of COPD is increasingly worldwide, which has caused the burden on individuals and society. This paper summarizes the pathogenesis of COPD and clarifies the effect and mechanism of the latest targeted drugs for COPD. Besides, we focus on NOD-like receptor thermal protein domain associated protein 3 inflammasome (NLRP3 inflammasome). NLRP3 can promote production of interleukin-1β (IL-1β) and interleukin-18 (IL-18). NLRP3 is an important factor in the migratory aggregation of macrophages and neutrophils and the generation of oxidative stress. Inhibition of NLRP3 inflammasome indirectly blocks the inflammatory effects of IL-1β and IL-18, which may be regarded as an ideal target for COPD treatment.

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“…Epithelial-mesenchymal interactions regulate lung development and restoration of alveolar architecture after lung injury [64]. In the presence of fibroblasts, ATII cells can give rise to alveolospheres in mice and humans [3].…”

Section: Mesenchymementioning

confidence: 99%

Impaired Alveolar Re-Epithelialization in Pulmonary Emphysema

Lin

Bahmed

Kośmider

2022

Cells

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Alveolar type II (ATII) cells are progenitors in alveoli and can repair the alveolar epithelium after injury. They are intertwined with the microenvironment for alveolar epithelial cell homeostasis and re-epithelialization. A variety of ATII cell niches, transcription factors, mediators, and signaling pathways constitute a specific environment to regulate ATII cell function. Particularly, WNT/β-catenin, YAP/TAZ, NOTCH, TGF-β, and P53 signaling pathways are dynamically involved in ATII cell proliferation and differentiation, although there are still plenty of unknowns regarding the mechanism. However, an imbalance of alveolar cell death and proliferation was observed in patients with pulmonary emphysema, contributing to alveolar wall destruction and impaired gas exchange. Cigarette smoking causes oxidative stress and is the primary cause of this disease development. Aberrant inflammatory and oxidative stress responses result in loss of cell homeostasis and ATII cell dysfunction in emphysema. Here, we discuss the current understanding of alveolar re-epithelialization and altered reparative responses in the pathophysiology of this disease. Current therapeutics and emerging treatments, including cell therapies in clinical trials, are addressed as well.

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Roles of Mesenchymal Cells in the Lung: From Lung Development to Chronic Obstructive Pulmonary Disease

Cited by 26 publications

References 190 publications

Single-cell transcriptomic characterization reveals the landscape of airway remodeling and inflammation in a cynomolgus monkey model of asthma

Single-cell transcriptomic characterization reveals the landscape of airway remodeling and inflammation in a cynomolgus monkey model of asthma

Pathological Mechanism and Targeted Drugs of COPD

Impaired Alveolar Re-Epithelialization in Pulmonary Emphysema

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