Psoriatic and rheumatoid arthritis joints differ in the composition of CD8+ tissue-resident memory T cell subsets
Giovanni A. M. Povoleri, Lucy E. Durham, Elizabeth H. Gray, Sylvine Lalnunhlimi, Shichina Kannambath, Michael J. Pitcher, Pawan Dhami, Thomas Leeuw, Sarah Ryan, Kathryn J. A. Steel, Bruce Kirkham, Leonie S. Taams
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.