InflammTswitch- MSC-mediated T-cell switch in rheumatoid arthritis

Rheumatoid arthritis is a common chronic inflammatory disease that affects 1% of the world population, with a higher incidence in women. Symptoms, including swelling, redness pain and stiffness, are caused by an abnormal activation of the innate and adaptive immune system and the subsequent increased production of pro-inflammatory cytokines and chemokines associated, which lead to damage in the joint tissue. Most treatments are limited to alleviate symptoms; thus, mesenchymal stem cells, showing high regenerative and immunomodulatory properties, serve as a novel therapeutic strategy. Benefits in the treatment of rheumatoid arthritis patients are controversial and potential effects of mesenchymal stem cell administration to disease progression have not been targeted so far. Based on the following, our central hypothesis is that, in response to the inflammatory environment in rheumatoid arthritis patients, the interaction of mesenchymal stem cells with T-cells is impaired resulting in the increased differentiation of inflammatory T-cells (inflammatory regulatory T-cells and senescent-like T-cells). Besides, mesenchymal stem cells can also actively contribute to disease progression through the activation of inflammatory signaling pathways initiated by the binding of RA-associated inflammatory factors accumulating in rheumatoid arthritis patients. This project aims to determine 1) the inflammatory factors associated with disease progression which could serve as promising candidates for RA treatment, 2) their long-term effects on MSC function in immunomodulation, and 3) their interaction with inflammatory T-cells accumulating in RA patients.