Fibroblast pathology in inflammatory diseases
Kevin Wei, Hung N. Nguyen, and Michael B. Brenner
Department of Medicine, Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Address correspondence to: Michael Brenner, Department of Medicine, Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Hale Building for Transformative Medicine, Room 6002Q, 60 Fenwood Road, Harvard Medical School, Boston, Massachusetts 02115, USA. Phone: 617.525.1001; Email: mbrenner@research.bwh.harvard.edu.
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Department of Medicine, Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Address correspondence to: Michael Brenner, Department of Medicine, Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Hale Building for Transformative Medicine, Room 6002Q, 60 Fenwood Road, Harvard Medical School, Boston, Massachusetts 02115, USA. Phone: 617.525.1001; Email: mbrenner@research.bwh.harvard.edu.
Find articles by Nguyen, H. in: JCI | PubMed | Google Scholar
Department of Medicine, Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Address correspondence to: Michael Brenner, Department of Medicine, Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Hale Building for Transformative Medicine, Room 6002Q, 60 Fenwood Road, Harvard Medical School, Boston, Massachusetts 02115, USA. Phone: 617.525.1001; Email: mbrenner@research.bwh.harvard.edu.
Find articles by Brenner, M. in: JCI | PubMed | Google Scholar
Published October 15, 2021 - More info
J Clin Invest. 2021;131(20):e149538. https://doi.org/10.1172/JCI149538.
© 2021 American Society for Clinical Investigation
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.
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