Molecular Imaging with Fibroblast Activation Protein Tracers depicts Inflammatory Joint Damage and its Transition to Resolution of Inflammation

ABSTRACT

Joint fibroblasts play an important role in the transition from joint inflammation to irreversible joint damage. There is no established clinical method to measure fibroblast activation during inflammation and their phenotypic dynamics upon therapy to date. Here we show that upon treatment with IL-17A/TNF-blocking antibodies fibroblasts change their phenotype from a destructive IL-6⁺/MMP3⁺THY1⁺ to a CD200⁺DKK3⁺ subtype, actively inducing resolution of inflammation. This phenotypic switch can be visualized due to so far unexplored different capacities of fibroblast subtypes with regard to receptor internalization of small molecular tracers with high affinity to FAP. Although FAP expression levels are comparable between fibroblast subtypes in the joint, FAP internalisation rate correlates with the destructive potential of fibroblasts and resolving fibroblasts have a lower FAP internalisation rate, providing a valuable imaging tool to visualize the transition from joint damage to resolution of inflammation.