Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and is characterized by uncontrolled inflammation of the synovial tissue, eventually leading to pain and joint destruction. RA is a complex disease resulting by a combination of genetic and environmental factors. The most profound genetic association exists within MHC-II genes suggesting that RA pathology is immune
(specifically Thelper) cell dependent. One of the strongest environmental risk factors for RA development is cigarette smoking. How smoking impacts the lung environment in genetically susceptible individuals in such a way that this eventually contributes to autoimmune joint pathology is largely unknown. We have recent evidence that cigarette smoking might trigger the formation of potentially pathogenic T cells in lungs of RA patients which were also found in inflamed joints of the same patients. The precise mechanisms behind this link between lung and joint inflammation are currently unknown. The goal of the current project is to explore the regional and systemic features of these immune cells and their link to RA onset. This will be achieved by a cellular and deep molecular exploration of a unique collection of patient samples and to look for the underlying disease mechanisms in an experimental model. Altogether, this study will lead to a better understanding of the earliest phases in RA development and could pave the path for more effective immune therapies.