Autoimmune rheumatologic diseases
Psoriatic arthritis (PsA) is a spondyloarthropathy affecting the joint and skin. Our lab previously showed high frequencies of IL-17+ CD8+ T-cells (Tc17) in PsA synovial fluid (SF), which correlate with clinical, serological and imaging measures of disease activity, and thus may contribute to PsA pathogenesis. Our aim is to functionally and molecularly characterise Tc17 cells to understand their role in PsA.
Since the frequency of Tc17 cells in human peripheral blood (PB) is very low (0.22±0.05%, n=16), we investigated Tc17 induction in vitro. Addition of rhIL-1β and IL-23 to healthy PB CD8+ T-cells cultured with α-CD3/28 beads for 3 days, led to a modest but significant increase in IL-17+ CD8+ T-cells (0.95±0.29%, p=0.0078, n=8). Addition of rhIL-6 or IL-2 did not lead to a further increase. We optimised an IL-17 secretion assay to sort these IL-17-secreting cells. Successful sorting was validated by ELISA (n=2). Sorted IL-17+ CD8+ T-cells were cultured for 24 hours and their supernatants added to synovial tissue fibroblasts. Addition of Tc17 (or Th17) cell culture supernatants enhanced IL-6 and IL-8 production by PsA synovial tissue fibroblasts compared to their IL-17-negative counterparts (n=2). These data indicate that in vitro generated IL-17+ CD8+ T-cells can exert pro-inflammatory activity.
We are currently translating these findings by investigating the pro-inflammatory capacity of synovial Tc17 cells from PsA patients, and determining their molecular phenotype. These data will provide novel insights into the contribution of Tc17 cells to the immunopathology of PsA.
Funded by a King's Health Schools studentship (MRC doctoral training grant).