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 E. Ryan,
Kathryn J.A. Steel,
Bruce W. Kirkham,
Leonie S. Taams
Affiliations
Giovanni A.M. Povoleri
Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London SE1 1UL, UK
Lucy E. Durham
Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London SE1 1UL, UK
Elizabeth H. Gray
Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London SE1 1UL, UK
Sylvine Lalnunhlimi
Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London SE1 1UL, UK
Shichina Kannambath
BRC Genomics Core, NIHR Biomedical Research Center, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, Guy’s Hospital, London SE1 9RT, UK
Michael J. Pitcher
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London SE1 9RT, UK
Pawan Dhami
BRC Genomics Core, NIHR Biomedical Research Center, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, Guy’s Hospital, London SE1 9RT, UK
Thomas Leeuw
Immunology & Inflammation Research TA, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany
Sarah E. Ryan
Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London SE1 1UL, UK
Kathryn J.A. Steel
Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London SE1 1UL, UK
Bruce W. Kirkham
Rheumatology Department, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK
Leonie S. Taams
Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London SE1 1UL, UK; Corresponding author
Summary: 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.
