The Fibro-Immune Landscape Across Organs: A Single-Cell Comparative Study of Human Fibrotic Diseases - PubMed
3 hours ago
- #immune-stromal crosstalk
- #fibrosis
- #single-cell RNA sequencing
- Fibrosis is a key feature in many solid cancers, influencing tumor progression, immune evasion, and treatment resistance.
- The study conducted an integrative single-cell RNA sequencing (scRNA-seq) analysis of fibrotic tissues from liver, lung, heart, and kidney, alongside non-fibrotic controls.
- Fibroblasts were the main ECM-producing cells in liver and lung, while endothelial-derived stromal populations dominated in heart and kidney.
- Immune profiling revealed distinct patterns: macrophages showed organ-specific polarization, T cells had tissue-resident subsets in lung and MAIT cells in liver, and B cells exhibited heterogeneity, including an interferon-responsive subset in pulmonary fibrosis.
- Gene set variation analysis (GSVA) identified divergent signaling programs across organs, such as TGF-β/TNF-α in heart, NOTCH/mTOR in kidney, glycolysis/ROS in lung, and KRAS/interferon pathways in liver.
- Cell-cell communication analysis highlighted interactions between macrophages, T/B cells, and stromal cells via collagen, laminin, and CXCL signaling.
- The study provides a cross-organ atlas of fibro-immune ecosystems, revealing shared and organ-specific mechanisms, with implications for precision anti-fibrotic therapy and biomarker development.