Research led by the University of Birmingham has found that re-purposing already existing drugs or combining therapies could be used to treat patients who have difficult to treat autoimmune diseases.
Funded by Versus Arthritis, the research was led by the University of Birmingham’s Institute of Inflammation and Ageing and is published in Proceedings of the National Academy of Sciences.
The research, a collaboration with the University of Oxford, University of Cambridge, University of York, Université Rennes in France, and the University of Lausanne in Switzerland, was supported by the National Institute for Health Research Birmingham Biomedical Research Centre.
Dr Saba Nayar, of the University of Birmingham, explains: “In this study, we found that fibroblasts - cells that play a critical role in shaping and supporting organ function - also play a key role in the process of the formation of tertiary lymphoid structures, which are small clusters of immune cells found at the sites of chronic inflammation.
“Inflammation is the body’s process of fighting against things that harm it, such as infections, injuries, and toxins, in an attempt to heal itself. When something damages cells, our bodies releases chemicals that trigger a response from our immune system.
“This response usually lasts for a few hours or days, however in chronic inflammation the response lingers, leaving the body in a constant state of alert. Chronic inflammation occurs in a range of conditions from cancer to arthritis and other autoimmune conditions - illnesses or disorders that occur when healthy cells get destroyed by the body's own immune system.”
Dr Joana Campos, also of the University of Birmingham, says: “Tertiary lymphoid structures play a key role in the progression of autoimmune conditions such as Sjögren's Syndrome - a disorder that affects parts of the body that produce fluids like tears and saliva.
“While the presence of active fibroblasts in tertiary lymphoid structures has been previously appreciated, our research has been able to demonstrate the functional changes that regulate fibroblasts’ ability to support a pathogenic response in the tissue and the signals responsible for these changes. Importantly, drugs against those cytokines have been already developed and used in other conditions, such as allergy.”
Senior Author and Principal Investigator Dr Francesca Barone, of the University of Birmingham, adds: “Our research has led us to conclude that we can target pathogenic fibroblasts and induce resolution of tissue inflammation by using drugs that have been already developed and are very safe.
“This means that those treatments can be used in patients with autoimmune conditions. This will be extremely useful both in patients with difficult to treat disease, when immune suppressive therapy has failed or in combination therapy, allowing doctors to reduce the dose and the side effects of immune suppressive toxic medication.
“Discovering that the programme responsible for tertiary lymphoid organ formation relies on signals previously considered ‘benign’ surprised us, but also enable us to think creatively to new ways to treat complex conditions such as Sjogren’s syndrome, that to date has had no cure.”
For more information please contact Emma McKinney, Communications Manager (Health Sciences), University of Birmingham, tel: +44 (0) 121 414 6681, or contact the press office on +44 (0) 7789 921 165.
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- Nayar et al (2019). ‘Immuno-fibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology’. Proceedings of the National Academy of Sciences.
- Authors of this research were Saba Nayar, Joana Campos, Charlotte Smith, Valentina Iannizzotto, David Gardner, Frédéric Mourcin, David Roulois, Jason Turner, Marvin Sylvestre, Saba Asam, Bridget Glaysher, Simon Bowman, Douglas Fearon, Andrew Filer, Karin Tarte, Sanjiv Luther, Benjamin Fisher, Christopher Buckley, Mark Coles and Francesca Barone.
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