Decoding Inflammatory Signals from the Extracellular Matrix for the Development of New Immunotherapies

An immune response to pathogen invasion is triggered upon detection of pathogenic molecules by innate immune sensors, whilst non‐infectious threat is signalled by endogenous inflammatory stimuli. Although insights into pathogen pattern recognition have revealed a great deal about the molecular basis of host defence against infection, it is not well understood how endogenous molecules activate immunity. Previous work revealed how extracellular matrix molecules specifically induced during tissue damage and cellular stress, or associated with tumorigenesis, create a pro‐inflammatory niche that enables resident stromal cells and infiltrating immune cells to survive and thrive, and within which matrix molecules directly activate site‐specific inflammatory programmes. Our new data detail how matrix molecules are recognized as inflammatory triggers, the distinct immune signalling pathways they activate, and the importance of identifying pathologically relevant forms of matrix constituents to understanding their contribution to inflammation. Current work focuses on translating these discoveries into novel diagnostic tools, and developing new drugs that target the microenvironment to enable selective amelioration of aberrant ‘sterile’ inflammation in autoimmune and fibrotic diseases, and to re‐educate immunity against tumors.