Research of my team is focused on the cellular and molecular pathways of IL-23/IL-17-immune axis in spondyloarthritis (SpA), a prevalent chronic rheumatic condition characterized by inflammation and abnormal new bone formation. Using gene expression profiling of SpA synovitis we identified a striking disease-specific myofibroblast signature and found that these synovial stromal cells express IL-23A in vivo and in vitro when exposed to cellular stress. Therefore we propose that stressed stromal cells can act as primary drivers of IL-23/IL-17-mediated tissue inflammation and remodelling. We are studying the function of stromal-derived IL-23A. In parallel we are investigating mechanisms of production and function of IL-17D, another stromal-derived member of IL-17 family.

The second line of research is devoted to understanding of the mechanisms regulating the breach of peripheral tolerance in rheumatoid arthritis (RA), chronic autoimmune disease where autoreactive B and T cells play a central role. Here we focused on the transcriptional co-activator Bob1. Based on our human and experimental data, we hypothesize that Bob1 contributes to RA pathogenesis by facilitating the generation of pathogenic T and B cells in RA synovium where they promote the broadening and maturation of the autoimmune response. We are studying function of Bob1 in human primary B and T cells in vitro and in vivo in experimental autoimmune arthritis, where we created a mouse with inducible overexpression of Bob1-targeted to B and/or T cells.