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Dendritic cells in the joint: One size does not fit all for rheumatoid arthritis

Trinity School of Medicine researchers provide unique insight into joint inflammation in patients with rheumatoid arthritis. Rheumatoid arthritis currently affects about 1% of the world’s population and about 2,000 new cases are diagnosed annually in Ireland. Patients suffering from rheumatoid arthritis require lifelong treatment. However, even with treatment they can suffer from joint destruction, pain, and disability, as well as depression, and social isolation. While treatments are improving, there is still a very real need to identify new treatment strategies, as unfortunately only one in every four patients reach full remission. Therefore, we need to better understand the complex cellular and molecular events that occur directly in the affected joints of patients with rheumatoid arthritis. This will enable a more directed approach to treating this autoimmune disease.

Dr Mary Canavan, Research Fellow in the Trinity Biomedical Sciences Institute was the first author in a paper recently published in Frontiers in Immunology which sought to explore the role of dendritic cells in the development of rheumatoid arthritis. Dendritic cells are a key immune cell in the body, and there are many different subtypes - each with its own unique role. Dr Canavan described the premise of the study:

To date, much of the work on dendritic cells in humans has been performed in blood as it is easy to access in sufficient quantities to perform experiments. In this study, we explored the role of a specific dendritic cell subtype, CD1c+ dendritic cells, in patients with rheumatoid arthritis. This was the first study of its kind to examine these dendritic cells, not only in peripheral blood, but at the site of inflammation, that is, in the affected joints of the patients with rheumatoid arthritis.”

The research team, led by Professor Ursula Fearon, Professor of Molecular Rheumatology in Trinity College Dublin, discovered that by using advanced techniques (multicolour flow cytometry and RNA sequencing) that CD1c+ dendritic cells migrate from the peripheral blood to the inflamed tissue in the joint (the synovium). Upon arrival into the synovium, these dendritic cells have unique proinflammatory and migratory gene signatures, while also expressing a diverse combination of multiple activation or maturation markers. These ‘poly maturational’ dendritic cells demonstrate for the first time how complex the activation spectrum of immune cells in the joint is, with cells residing across a diverse continuum of activation. Dr Canavan explained the significance of these findings:

This no doubt has consequences for neighbouring cells in joint, such as T cells. Moreover we demonstrated that this CD1c+ dendritic cell population produces large amounts of ‘matrix degrading enzymes’ which can destroy cartilage and bone. Therefore, this study provides unique and previously unexplored insights into the complex role dendritic cells may have in joint inflammation in patients suffering from rheumatoid arthritis.”

This research was funded by the Centre for Arthritis Ireland, Arthritis Ireland, and the American Association of Immunologists. Janssen Research and Development (PA, United States) were key collaborators, as well as the Department of Orthopaedics and the European League Against Rheumatism (EULAR) Centre of Excellence (both in St Vincent’s Hospital, Dublin), Department of

Orthopaedics, University College Dublin, and the Department of Rheumatology, Tallaght University Hospital.

The study full-text can be accessed here: https://www.frontiersin.org/articles/10.3389/fimmu.2021.745226/full