Grant: Project Grant

Rheumatoid arthritis (RA) affects 1 out of every 100 adult Canadians. That's about 300,000 Canadians. Anyone can get RA and at any age. RA affects women two to three times more often than men. RA is an autoimmune disease. Autoimmune diseases are illnesses that occur when the body's tissues are mistakenly attacked by their own immune cells. RA causes chronic inflammation of the joints and can lead to their loss of function. In addition, inflammation in RA can also damage other parts of the body (e.g., lungs, heart, eyes, blood vessels). As a result, RA not only significantly impacts the quality of life of patients but also shortens their lifespan. This highlights the importance of effectively treating RA by suppressing inflammation (i.e. treatment target). A major problem is that despite of all current treatment options, some RA patients don't reach the treatment target. Understanding the mechanisms that drive inflammation in RA is the only way to provide new therapeutic options for those patients. We are specifically interested in hematopoietic stem and progenitor cells (HSPCs) as these are the cells that give rise to most immune cell-types. We have shown that in RA, HSPCs are dysfunctional. Now we propose to study samples from RA patients to address the following questions: 1- Do HSPCs from RA patients promote inflammation?; 2- Are the HSPC-defects in RA patients transferred to the immune cells that are generated from HSPCs?; and 3- Does RA treatment restore the defects of HSPCs in RA patients? Three scientists: Dr. Nijnik - an expert in HSPCs and in mouse models of immune disorders; Dr. Colmegna - a rheumatologist clinician and HSPC scientist; and Dr. Langlais - an expert in immune cells' gene regulation will work together: (1) to accelerate the understanding of the role of HSPCs in RA, and (2) to uncover new therapeutic targets for RA patients.