Project 454412

Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes joint pain and bone destruction. It is a leading cause of disability in Canada. There is no cure, only treatments that temporarily relieve symptoms. Many patients do not improve with currently available treatments. A better understanding of how RA develops in the joints is needed to improve treatment strategies. We know that immune cells in the joints communicate with fibroblasts (cells that produce structural compounds like collagen) to drive inflammation. We also know that the functions of these cells are controlled by differences in cellular energy production, known as cell metabolism. But it is unknown how metabolism is altered in fibroblasts in the joint and how this affects immune cell behaviour in RA. Our goals are to (1) understand how metabolism underlies fibroblast-immune cell communication in the joints and (2) relate this to RA progression and treatment response. To do this, we have developed a new imaging technology that can simultaneously define the different features of immune cells, fibroblasts, and their metabolism in tissue samples. We will examine joint tissues from patients with RA to (1) determine how fibroblast metabolism is altered, and how this affects immune cell function. We will then (2) look at whether these features can predict whether patients improve with different treatments for RA. Ultimately, this work will help personalize treatment options for patients with RA.