MicroRNAs as regulators of cross-talk between cells in rheumatoid arthritis synovium

• Applicant: Dr. Florian Meier
• Subject Area: Rheumatology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 234628656

In rheumatoid arthritis (RA), cross-talk of immune cells in the synovium is pivotal for initiation and perpetuation of the inflammation. While originally only regarded as mediators in the fine-tuning of the immune response, current data suggest an important proinflammatory role for microRNAs (miRs) such as miR-155 in clinical and experimental arthritis. Furthermore, distinct miRs are associated with disease activity in RA. Recent studies described that miRs can be transferred from cell to cell by microparticles (MPs). Hence, it is of great interest to understand the contribution of MP-associated miR transfer to the cross-talk of key immune cells in RA in detail, namely T cells, monocytes and fibroblast-like synoviocytes (FLS). The first aim of the project is to elucidate miR expression by T cells and monocytes and by MPs derived from these cells during specific endogenous activation using next-generation sequencing. Next, MP transfer between T cells, monocytes and FLS will be visualized by fluorescence microscopy. Finally, demonstration of real-time exchange of specific and relevant miRs, e.g. miR-155, and determination of their functional relevance to the recipient cell is sought.The complex miR network has arisen as a new and interesting field in autoimmunity and several reports have shown intriguing relevance in the pathophysiology of RA. A better understanding of the complex regulatory interactions between the cells of RA synovial tissue with regard to miRs and miR transfer will not only provide a deeper insight into RA pathophysiology but also facilitate the development of novel therapeutic strategies. Synthetic MPs may therefore be ideal vehicles for the transport of anti-inflammatory miRs or antagonistic miRs, so-called antagomirs, to specific cell types.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Iain B. McInnes