Fibroblasts in immune-mediated inflammatory diseases: The soil of inflammation.

As one of the most abundant stromal cells, fibroblasts are primarily responsible for the production and remodeling of the extracellular matrix. Traditionally, fibroblasts have been viewed as quiescent cells. However, recent advances in multi-omics technologies have demonstrated that fibroblasts exhibit remarkable functional diversity at the single-cell level. Additionally, fibroblasts are heterogeneous in their origins, tissue locations, and transitions with stromal cells. The dynamic nature of fibroblasts is further underscored by the fact that disease stages can impact their heterogeneity and behavior, particularly in immune-mediated inflammatory diseases such as psoriasis, inflammatory bowel diseases, and rheumatoid arthritis, etc. Fibroblasts can actively contribute to the disease initiation, progression, and relapse by responding to local microenvironmental signals, secreting downstream inflammatory factors, and interacting with immune cells during the pathological process. Here we focus on the development, plasticity, and heterogeneity of fibroblasts in inflammation, emphasizing the need for a developmental and dynamic perspective on fibroblasts.