Details

Autor(en) / Beteiligte

• Korsunsky, Ilya
• Wei, Kevin
• Pohin, Mathilde
• Kim, Edy Y
• Barone, Francesca
• Major, Triin
• Taylor, Emily
• Ravindran, Rahul
• Kemble, Samuel
• Watts, Gerald F M
• Jonsson, A Helena
• Jeong, Yunju
• Athar, Humra
• Windell, Dylan
• Kang, Joyce B
• Friedrich, Matthias
• Turner, Jason
• Nayar, Saba
• Fisher, Benjamin A
• Raza, Karim
• Marshall, Jennifer L
• Croft, Adam P
• Tamura, Tomoyoshi
• Sholl, Lynette M
• Vivero, Marina
• Rosas, Ivan O
• Bowman, Simon J
• Coles, Mark
• Frei, Andreas P
• Lassen, Kara
• Filer, Andrew
• Powrie, Fiona
• Buckley, Christopher D
• Brenner, Michael B
• Raychaudhuri, Soumya

Titel

Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases

Ist Teil von

• Med (New York, N.Y. : Online), 2022-07, Vol.3 (7), p.481-518.e14

Ort / Verlag

United States

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Pro-inflammatory fibroblasts are critical for pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren's syndrome and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited our understanding of which pathways are shared by multiple diseases. We profiled fibroblasts derived from inflamed and non-inflamed synovium, intestine, lungs, and salivary glands from affected individuals with single-cell RNA sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes. Two shared clusters, CXCL10 CCL19 immune-interacting and SPARC COL3A1 vascular-interacting fibroblasts, were expanded in all inflamed tissues and mapped to dermal analogs in a public atopic dermatitis atlas. We confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation. This work represents a thorough investigation into fibroblasts across organ systems, individual donors, and disease states that reveals shared pathogenic activation states across four chronic inflammatory diseases. Grant from F. Hoffmann-La Roche (Roche) AG.