Abstract Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases with a frequency of 0.5–1.0% in the adult population of developed countries. RA is characterized by an aberrant inflammation of the synovial membrane that causes irreversible joint and bone damages. It has been previously described that regulatory T cells (Tregs) were defective in RA patients and that whereas Treg depletion increased the severity of the disease, Treg transfer efficiently reversed this effect in the collagen-induced arthritis (CIA) model, an animal model of RA. These studies strongly suggest that Treg therapy may be able to treat RA patients by inducing a long-term restoration of appropriate tolerance. Moreover, adding Ag-specificity to the expanded Tregs may promote their migration to the site of the abnormal inflammation and enhance their function. The aim of our study has been to engineer and expand chimeric antigen receptor (CAR)-expressing Tregs specifically targeting an antigen present in the joint of RA patients to induce a localized and effective immunosuppressive response. We developed a CAR directed against citrullinated vimentin (CV), a posttranslational modified intermediate filament protein known to be exclusively located in the extracellular matrix of the synovial tissue in 50% of the RA patients. We are currently working on transducing the CV-specific CAR into Tregs to then study the functional activity of these cells in vitro. We are also developing an in vivo protocol to assess the therapeutic efficacy of the CAR Treg transfer in CIA model. In conclusion, our project aiming to combine Treg therapy and CAR technology may lead to the development on a promising therapeutic tool to cure RA and potentially other autoimmune disorders.