Rheumatic diseases affect up to 60% of the 120-million EU-citizens, at an estimated cost of €240-billion with direct costs of 2%EU-GDP. Inflammatory-Arthritis(IA), including Rheumatoid-Arthritis(RA) and Psoriatic-Arthritis(PsA) cause significant joint destruction, disability, increased mortality and are associated with co-morbidities leading to a severe impact on the productivity and quality of life of over 40.000 people in Ireland. While novel biotherapeutics have improved management of IA, there are no cures. Furthermore, it is impossible to predict who will develop severe, erosive disease or who will respond to treatment thus patients are subjected to several rounds of “exploratory” treatments until the right treatment is identified. Importantly, this results in severe debilitating trauma for the patients.
CrossTalk is an interdisciplinary study that utilises state-of-the-art technologies in order to identify novel opportunities for targeted therapeutic intervention and improved patient stratification.
Until recently, T-cells were divided into well-defined subsets, identified by the expression of a key cytokine. There is growing appreciation that T-cells exhibit polyfunctionality by producing multiple cytokines simultaneously. However, under the “wrong” environmental circumstances, polyfunctional T-cells(poly-T) can drive autoimmune-disease pathogenesis. I have shown that synovial tissue poly-T-cells can predict RA-patient stratification, correlate with disease progression in RA and PsA and importantly, are present at the joints of at risk-individuals prior to the development of clinical-inflammation. Therefore, poly-T cells are significant initiators and propagators of synovial inflammation. However, it remains unclear (i)how they accumulate to the joint and (ii)how their interaction with immuno-active synovial-fibroblasts leads to the differential pathology of RA and PsA.
Identification of chemokine receptor repertoires associated with joint poly-T cells can lead to early targeted therapeutic interventions and improved patient stratification while, understanding the T-cell-synovial fibroblast crosstalk, will result in specific targeting of inflammatory pathways and novel therapies.
CrossTalk will lead to significant advances in clinical practice and improved outcomes for patients.
