Targeting fibroblasts in immune mediated inflammatory diseases: a cellular basis for cure?

Fibroblasts constitute a major component of our stroma, the supportive bedding in which our tissues reside. The introduction of advanced single-cell technologies has greatly enhanced our appreciation of fibroblast heterogeneity in health and immune-mediated inflammatory diseases (IMIDs). This heterogeneity correlates with their diverse functions, including providing architectural support, tissue identity, 'stromal memory', and regulating immune responses and fibrosis. In RA, fibroblasts contribute to both synovial inflammation and bone and cartilage damage, and in IBD to loss of the epithelial barrier, intestinal inflammation, and the development of intestinal strictures and fistulae in Crohn's disease. Fibroblasts have also been associated with non-response to current biologic therapies in RA and IBD. Targeting pathogenic fibroblast populations using new therapeutic modalities such as Chimeric Antigen Receptor (CAR) T-cell therapies may 'reset' the stroma back to health and give hope for cure in these debilitating IMIDs.