The Role of Fibroblasts Across Inflammation and Immunity

Fibroblasts have been canonically considered as extracellular matrix organizing cells but are now recognized as active participants in immune regulation and tissue homeostasis. In the context of fibrosis, fibroblasts are a well-understood contributor to global morbidity and mortality across cardiac, pulmonary, renal, and hepatic tissue. Beyond this, the fibroblast is a key contributor to barrier immunity and stem cell niche formation and a determinant of vascular permeability, yet it is also capable of lymphocyte homeostasis in the context of lymphoid tissue regulation. Here, we explore the role of fibroblasts across acute and chronic inflammation and their relationship to innate and adaptive immune elements, through the lens of immune-mediated inflammatory diseases. Together, the diversity of fibroblast functions presents a therapeutic challenge, but one with the potential to restore inflamed tissue to health. We discuss novel approaches driven by technological developments that now make immunotherapeutic interventions targeting fibroblasts increasingly possible.