Psoriatic and rheumatoid arthritis joints differ in the composition of CD8+ tissue-resident memory T cell subsets

Abstract

CD69+CD103+ tissue-resident memory T (T_RM) cells are important drivers of inflammation. To decipher their role in inflammatory arthritis, we apply single-cell, high-dimensional profiling to T cells from the joints of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identify three groups of synovial CD8+CD69+CD103+ T_RM cells: cytotoxic and regulatory T (Treg)-like T_RM cells are present in both PsA and RA, while CD161+CCR6+ type 17-like T_RM cells with a pro-inflammatory cytokine profile (IL-17A+TNFα+IFNγ+) are specifically enriched in PsA. In contrast, only one population of CD4+CD69+CD103+ T_RM cells is detected and at similarly low frequencies in both diseases. Type 17-like CD8+ T_RM cells have a distinct transcriptomic signature and a polyclonal, but distinct, TCR repertoire. Type 17-like cells are also enriched in CD8+CD103- T cells in PsA compared with RA. These findings illustrate differences in the immunopathology of PsA and RA, with a particular enrichment for type 17 CD8+ T cells in the PsA joint.

Keywords: CD103; CD8+ T cells; CP: Immunology; CyTOF; T(RM); Tc17 cells; joint; psoriatic arthritis; rheumatoid arthritis; scRNA-seq; synovial fluid.