Fibroblast pathology in inflammatory diseases

Fibroblasts are important cells for the support of homeostatic tissue function. In inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, fibroblasts take on different roles (a) as inflammatory cells themselves and (b) in recruiting leukocytes, driving angiogenesis, and e...

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Bibliographic Details
Published in:The Journal of clinical investigation 2021-10, Vol.131 (20)
Main Authors: Wei, Kevin, Nguyen, Hung N, Brenner, Michael B
Format: Article
Language:English
Subjects:
Arthritis, Rheumatoid - pathology
Cell Differentiation
Development and progression
DNA Methylation
Fibroblasts
Fibroblasts - classification
Fibroblasts - pathology
Fibroblasts - physiology
Genetic aspects
Health aspects
Humans
Inflammation
Inflammatory bowel diseases
Inflammatory Bowel Diseases - pathology
Physiological aspects
Review
Rheumatoid arthritis
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Summary:Fibroblasts are important cells for the support of homeostatic tissue function. In inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, fibroblasts take on different roles (a) as inflammatory cells themselves and (b) in recruiting leukocytes, driving angiogenesis, and enabling chronic inflammation in tissues. Recent advances in single-cell profiling techniques have transformed the ability to examine fibroblast states and populations in inflamed tissues, providing evidence of previously underappreciated heterogeneity and disease-associated fibroblast populations. These studies challenge the preconceived notion that fibroblasts are homogeneous and provide new insights into the role of fibroblasts in inflammatory pathology. In addition, new molecular insights into the mechanisms of fibroblast activation reveal powerful cell-intrinsic amplification loops that synergize with primary fibroblast stimuli to result in striking responses. In this Review, we focus on recent developments in our understanding of fibroblast heterogeneity and fibroblast pathology across tissues and diseases in rheumatoid arthritis and inflammatory bowel diseases. We highlight new approaches to, and applications of, single-cell profiling techniques and what they teach us about fibroblast biology. Finally, we address how these insights could lead to the development of novel therapeutic approaches to targeting fibroblasts in disease.
ISSN:1558-8238
0021-9738
1558-8238
DOI:10.1172/jci149538