AxSpA joint tissue is characterised by HLA-DR+ tissue resident memory (TRM) and killer cell immunoglobulin-like receptor (KIR)+ CD8+ T cell subsets

Abstract

ObjectiveAxial Spondyloarthritis (AxSpA) is a common inflammatory arthritis with HLA-B*27 as the major genetic risk. Recent discoveries of AxSpA-specific T cell receptor (TCR) motifs and the self and bacterial peptides that they recognize support a pathogenic role of CD8+ T cells. Despite of previous work on synovial fluid, the characteristics of CD8 cells in joint tissue are currently unknown. MethodSynovial tissues from 5 AxSpA patients were used for single cell RNA sequencing (scRNA-seq). Paired TCR sequencing was carried out for 2. The abundance of KIR+CD8+ T cells in the blood from 9 AxSpA patients and 10 healthy controls was measured using flow cytometry. The expression of naive and memory T cell markers (CCR7, CD45RA and CD45RO) were compared between KIR+ and KIR- CD8 cells. ResultsWe observed conventional, TRAV1-2+ mucosal-associated invariant T (MAIT) cell and MKI67+ proliferating cell populations in synovium. Following sub-clustering of conventional CD8+ T cells, HLA-DR+ tissue resident memory (TRM), circulating, KIR+ and FCGR3A+ (encoding CD16) cell subsets were observed. HLA-DR+ TRM and KIR+ cells were clonally expanded and exhibited distinct transcriptional features, enriched for T cell activation pathways and natural killer (NK) cell-mediated cytotoxicity pathway respectively. Lastly, KIR+CD8+ T cells were increased in AxSpA blood and enriched for CD45RA+CCR7- TEMRA cells. ConclusionHere we present the very first transcriptomic profiling of CD8+ T cells in synovium tissue and highlight potential roles of HLA-DR+ TRM and KIR+ cells in AxSpA pathology. This study adds novel insights to the disease mechanisms and offers new therapeutic opportunities.