Rheumatoid arthritis

Comparative Transcriptional Profiling of Key Macrophage and Fibroblast Subpopulations in Rheumatoid Arthritis–Associated Lung Disease

Arthritis RheumatolPublished Mechanistic study

Authors' conclusion

Flex scRNA-seq of pulmonary macrophage and fibroblast subpopulations reveals key differences in transcriptional profile, distinguishing RA-ILD from RA lung nodules. Parallel comparison of cell type-specific gene expression profiles between RA-ILD and IPF demonstrates significant overlap in profibrotic transcriptional programs.

Study context

Population
Lung tissue specimens from patients with RA-associated ILD (RA-ILD) or rheumatoid arthritis (RA) lung nodules and controls without disease
Comparison
RA-ILD vs RA lung nodules; RA-ILD vs idiopathic pulmonary fibrosis (IPF)
  • Controlsn = 4reference
  • RA-ILDn = 9
  • RA nodulesn = 3
Outcome
Gene expression profiles in macrophage and fibroblast populations contributing to tissue remodeling in RA-ILD vs RA lung nodules
Methodological detailsprobe-based Flex single-cell RNA sequencing (scRNA-seq) of fixed lung tissue specimens
  • Probe-based Flex scRNA-seq of fixed lung tissue specimens

Main finding

As reported in the abstract

  • Clustering profiles mirrored UMAP distributions from conventional poly(A) capture-based scRNA-seq of RA-ILD, IPF and control lung tissue
  • RA-ILD vs RA lung nodules: only partial overlap; up-regulation of immunoregulatory, angioregulatory and matrix assembly pathways in RA-ILD fibroblasts
  • Selective up-regulation of pathways promoting innate and adaptive immunity in macrophage populations of RA lung nodules
  • RA-ILD vs IPF macrophages and fibroblasts: significant enhancement of profibrotic gene expression in both disease states

Original publication

Comparative Transcriptional Profiling of Key Macrophage and Fibroblast Subpopulations in Rheumatoid Arthritis–Associated Lung Disease. Arthritis Rheumatol. Published 22 June 2026. doi:10.1002/art.70256

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