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The Upper Bronchial Tract Mycobiome in COPD

ABSTRACT: The Upper Bronchial Tract Mycobiome in COPD

PROVIDER: PRJEB10645 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	ERR996425.fastq.gz	Fastqsanger.gz
	ERR996426.fastq.gz	Fastqsanger.gz
	ERR996431.fastq.gz	Fastqsanger.gz

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Project description:Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma. Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM). To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals. By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM. The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients.

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Short-range interactions between fibrocytes and CD8+ T cells in COPD bronchial inflammatory response

Project description:The peri-bronchial zone of chronic obstructive pulmonary disease (COPD) is the site of extensive infiltration of immune cell, allowing persistent contacts between resident cells and immune cells. Tissue fibrocytes interaction with CD8+ T cells and its consequences were investigated. We show that fibrocytes and CD8+ T cells are found in vicinity in distal airways and that potential interactions are more frequent in tissues from COPD patients compared to those of control subjects. Increased proximity and clusterization between CD8+ T cells and fibrocytes are associated with altered lung function. Tissular CD8+ T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. CD8+ T cells establish short-term interactions with fibrocytes, that trigger CD8+ T cell proliferation in a CD54- and CD86-dependent manner, pro-inflammatory cytokines production, CD8+ T cell cytotoxic activity and fibrocyte immunologic signaling. We defined a computational model describing these intercellular interactions and calibrated the parameters based on our experimental measurements. We showed the model’s ability to reproduce histological ex vivo characteristics, and observed major contributions of fibrocyte-mediated CD8+ T cell proliferation and fibrocyte death in COPD development. Using the model to test therapeutic scenarios, we predicted a recovery time of several years, and the failure of targeting independently chemotaxis or interacting processes. Altogether, our study reveals that local interactions between fibrocytes and CD8+ T cells can occur in vivo and could jeopardize the balance between protective immunity and chronic inflammation in bronchi of COPD patients.

2023-07-28 | PXD041402 | Pride

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