The Spectrum of Fibroblast Immune Biology

Recent advancements in single-cell omic technology and lineage-tracing approaches have established that functional and dysfunctional activities of the immune system are critically influenced by context-specific microenvironmental factors. Among stromal cells, fibroblasts are emerging as far more plastic and heterogeneous than previously appreciated, and an abundance of profound and unique connections with the functioning of distinct branches of the immune system and with the regulation of inflammatory processes in tissue homeostasis and pathological conditions have been revealed. In this article, we review the state-of-the-art in the biology of inflammatory fibroblasts, with a particular emphasis on their involvement in regulating, and in turn their regulation by, cells of the innate and adaptive immune systems in chronic nonmalignant diseases. We cover their ontogeny and distribution across tissues and their shared and unique transcriptional, biochemical, and immunological characteristics within distinct chronic inflammatory diseases, infections, and autoimmune conditions.