Finally, we address how these insights could lead to the development of novel therapeutic approaches to targeting fibroblasts in disease.Ĭardiac lymphatics have emerged as a therapeutic target in cardiovascular diseases to limit myocardial edema and inflammation, notably after myocardial infarction (MI). We highlight new approaches to, and applications of, single-cell profiling techniques and what they teach us about fibroblast biology. 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. 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. These studies challenge the preconceived notion that fibroblasts are homogeneous and provide new insights into the role of fibroblasts in inflammatory pathology. 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. 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. Fibroblasts are important cells for the support of homeostatic tissue function.
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