Professor of Immune Regulation & Inflammation King's College London London, England, United Kingdom
Abstract Text: The immunopathology of psoriatic arthritis (PsA) is driven in part by IL-17A. IL-17A production is typically attributed to conventional CD4+ and CD8+ T-cells, however unconventional innate-like T-cells including MAIT, iNKT and γδT-cells can be additional sources of IL-17A as well as IL-17F. We determined IL-17A and IL-17F expression in conventional and unconventional T-cells from PsA synovial fluid (n=7). Mass cytometry was performed on untreated or 3-hour PMA/ionomycin/GolgiStop stimulated CD3+ T-cells, and samples were analysed using a customised CATALYST pipeline.
FlowSOM clustering revealed that the dominant synovial T-cell populations were CD4+ (53%) and CD8+ conventional T-cells (39%), with lower frequencies of unconventional γδT-cells (2.1%) and CD8+ MAIT cells (4.6%). Very low frequencies of TCRVα24-Jα18 expressing iNKT-cells (0.6%) were found. Synovial IL-17A+ T-cells were predominantly found within CD8+ (51%) and CD4+ (48%) T-cells and characterised by high CXCR6 expression, with the majority of IL-17A+CD8+ T-cells displaying a CD103+ tissue-resident memory (TRM) phenotype. On average, 1.5% of IL-17A+CD8+ T-cells co-expressed high levels of TCRVα7.2 and CD161, suggestive of MAIT cells. Very few IL-17F producing T-cells were identified; these cells co-expressed IL-17A and clustered as conventional CD8+ TRM cells or CD4+ T-cells. We detected only sporadic TCRγδ or TCRVα24-Jα18 expressing cells amongst synovial IL-17 producing T-cells.
Our data indicate that synovial IL-17A and IL-17F production is predominantly confined to conventional CD4+ and CD8+ T-cells including TRM cells. High CXCR6 expression on PsA synovial IL-17-expressing T-cells suggests a functional role for the CXCR6-CXCL16 axis in recruitment or retention of these cells in the inflamed joint.
