Fibroblast Plasticity in Inflammation of the Barrier

ABSTRACT Barrier tissues such as skin, gut, and lung are critical for maintaining homeostasis and preventing pathogen invasion. However, they constantly face microbial, environmental, and mechanical challenges. Fibroblasts, the primary mesenchymal cells within these tissues, are no longer seen as passive structural elements. They show tremendous heterogeneity and plasticity beyond their conventional role, allowing them to act as active immune participants in inflammation. As an immune participant, fibroblasts are capable of undergoing phenotypic alterations in pathological conditions. They are able to release signaling molecules including chemokines and cytokines, remodel extracellular matrix, or even present antigens. The inflammatory landscape is thus shaped. This review integrates recent advances in exploring fibroblast plasticity in barrier inflammation. We summarize their roles in initiating, progressing and resolving inflammatory responses across the skin, gut and respiratory tract. Specific focus is placed on fibroblast–immune cell interactions, key signaling pathways, and the roles of specific subsets in inflammatory conditions. By integrating what has been investigated from single‐cell and multi‐omics analyses, this article highlights fibroblasts as both essential mediators of barrier inflammation and promising targets for targeted treatment.