Grant: Project Grant

Cigarette smoking is a major risk factor for the development of Rheumatoid Arthritis (RA), a common and debilitating autoimmune arthritis. Although smoking rates have reduced in the last several decades, smoking is still common in First Nations living in Canada. Notably, First Nations peoples have higher rates of RA compared to non-First Nations. This is primarily due to genetic risk, but interactions between gene and environment often heightens this risk. In spite of this, it is not known precisely how cigarette smoking leads to RA. In this proposal, our diverse research team will investigate the way cigarette smoking interacts with the immune system. Specifically, we think that neutrophils, which are an immune cell, are prone to inflammation that might lead to abnormal immune responses in people who are at high risk for RA development. We will investigate these interactions in neutrophils which are obtained from humans. We will also use a mouse model called collagen-induced arthritis, which aims to mimic what we observe in humans. Finally, we plan to study human samples from individuals who are at high risk to develop RA, specifically first-degree relatives of RA patients. We are going to try to help these relatives stop smoking, if they are continuing to do so. This may lower their risk of developing RA, but even if it does not, there are likely other health benefits of helping people quit smoking. Overall, we hope to better understand why and how RA begins, and improve the overall health of First Nations living in Manitoba.