Single-Cell Analysis Identifies Factors Associated with Rheumatoid Arthritis-Related Interstitial Lung Disease in...

Area of Science:

• Immunology
• Pulmonology
• Rheumatology

Background:

• Interstitial lung disease (ILD) is a serious manifestation of rheumatoid arthritis (RA).
• RA-associated ILD (RA-ILD) can mimic idiopathic pulmonary fibrosis (IPF), but their underlying immunologic and molecular mechanisms remain unclear.
• Understanding these mechanisms is crucial as RA-ILD and IPF have different treatment and progression patterns.

Purpose of the Study:

• To investigate the distinct immunologic and molecular mechanisms of RA-ILD and IPF at the single-cell level.
• To compare the transcriptional profiles of peripheral immune cells in RA-ILD and IPF patients.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells (PBMCs) from five RA-ILD patients and five IPF patients.
• Analysis focused on immune cell composition and gene expression patterns.

Main Results:

• scRNA-seq data from 31,416 immune cells revealed similar overall immune composition between RA-ILD and IPF.
• RA-ILD PBMCs showed elevated Natural Killer (NK) cells with increased cytotoxic and interferon-related gene expression.
• IPF PBMCs exhibited enrichment of CD16+ monocytes in TGF-β-driven fibrotic signaling pathways, with upregulation of fibrosis-related genes.

Conclusions:

• RA-ILD and IPF share peripheral immune cell similarities but display distinct transcriptional activation patterns.
• RA-ILD is characterized by enhanced NK-cell-mediated cytotoxic and interferon responses, alongside interferon-activated monocytes.
• IPF is characterized by a TGF-β-dominant fibrotic program involving CD16+ monocyte activation and increased fibrosis-related gene expression.