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Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis

ABSTRACT: Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis

PROVIDER: PRJNA978083 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24783206.fastq.gz	Fastqsanger.gz
	SRR24783207.fastq.gz	Fastqsanger.gz
	SRR24783208.fastq.gz	Fastqsanger.gz
	SRR24783209.fastq.gz	Fastqsanger.gz
	SRR24783210.fastq.gz	Fastqsanger.gz

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Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis

Project description:Rationale: Changes in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF). Objectives: To provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Methods: Peripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5’ single-cell RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations of Regulatory T-cells (Tregs) and Monocytes chemoattractants were measured in plasma and lung homogenates from patients and controls. Measurements and Main Results: Thirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations, corresponding to all expected peripheral blood cell populations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive IPF (1.8% vs 1.1%, p=0.007), and were associated with decreased survival (P=0.009 in Kaplan-Meier analysis). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Tregs were also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. Conclusions: The single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).

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Project description:The pathogenesis of idiopathic pulmonary fibrosis is multifactorial and characterized by progressive fibrosis and excessive accumulation of extracellular matrix in the interstitium of the lung, and driven by an imbalance between anti-fibrotic and pro-fibrotic factors leading to collagen deposition. In the present study we wanted to identify proteins involved in these processes, and performed high-resolution proteomic profiling of bronchoalveolar lavage (BAL) from IPF patients and controls. The proteomic analysis of BAL demonstrated that the complement system was highly differentially regulated in IPF patients as compared with controls.

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