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

CD69+CD103+ tissue-resident memory T (TRM) 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+ TRM cells: cytotoxic and regulatory T (Treg)-like TRM cells are present in both PsA and RA, while CD161+CCR6+ type 17-like TRM 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+ TRM cells is detected and at similarly low frequencies in both diseases. Type 17-like CD8+ TRM 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. [Display omitted] •Human arthritic joints contain distinct subsets of resident memory T (TRM) cells•Psoriatic and rheumatoid arthritis joints differ in TRM subset composition•Psoriatic arthritis is enriched for pro-inflammatory type 17 TRM and other T cells•Rheumatoid arthritis is enriched for T cells with a cytotoxic profile Combining CyTOF and scRNA-seq immunophenotyping, Povoleri et al. reveal quantitative differences in synovial CD8+ tissue-resident memory T (TRM) cell subset composition between psoriatic and rheumatoid arthritis. The proinflammatory type 17 profile enriched in TRM cells from psoriatic arthritis joints may potentially explain the differential responses to IL-17 blockade between the diseases.