TOP grant, 2018: € 675.000

Characterisation of the Immunomodulatory Effect of Stromal Cells in Health and Disease

Rheumatoid arthritis (RA) is a prototypic inflammatory autoimmune disease targeting synovial joints, with a prevalence of ~2% in the Netherlands and a higher incidence in females. Given the destructive nature of the disease, early diagnosis and start of treatment is extremely important. The production of autoantibodies can be detected already years before onset of RA, enabling the identification of seropositive individuals at risk of developing RA. In this project we aim to determine which molecules are involved in LN-SC-mediated control of autoreactive lymphocytes during health and disease using a mice-to-man approach. The combination of the unique expertise’s of both labs, in which the Mebius lab has the methods to analyze antigen presentation by LN-SC in an antigen-specific manner in mice and the van Baarsen lab has the ability to collect, culture and analyze LN-SC from healthy individuals, RA-risk individuals and RA patients, allows for a truly translational pproach. By combining state-of-the-art technologies, (transgenic) mouse models and unique patient materials, we will reveal which molecular pathways and modes of antigen presentation in LN-SC are instrumental in T-cell mediated B-cell activation and whether these processes are aberrant already during the earliest phases of RA.