Tissue-Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis

Arthritis Rheumatol. 2021 Jul;73(7):1220-1232. doi: 10.1002/art.41652. Epub 2021 May 25.

Abstract

Objective: To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA.

Methods: In-depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high-throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis.

Results: Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin-17A (IL-17A) and IL-22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin-homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up-regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function.

Conclusion: Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development.

MeSH terms

  • Adult
  • Aminopeptidases / genetics
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Arthritis, Psoriatic / genetics
  • Arthritis, Psoriatic / immunology*
  • Arthritis, Psoriatic / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors / genetics
  • GATA3 Transcription Factor / genetics
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunologic Memory / immunology
  • Immunophenotyping
  • Integrin alpha Chains / genetics
  • Interleukin-17 / immunology
  • Interleukins / immunology
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Oligosaccharides / metabolism
  • Psoriasis / genetics
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Receptor, Interferon alpha-beta / genetics
  • Receptors, CCR10 / metabolism
  • Receptors, CCR4 / metabolism
  • Sialyl Lewis X Antigen / analogs & derivatives
  • Sialyl Lewis X Antigen / metabolism
  • Skin / immunology*
  • Skin / pathology
  • Spondylarthropathies / genetics
  • Spondylarthropathies / immunology
  • Spondylarthropathies / pathology
  • Synovial Fluid / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • 6-sulfo sialyl Lewis X
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CCR10 protein, human
  • CCR4 protein, human
  • CD226 antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • IFNAR1 protein, human
  • IL17A protein, human
  • Integrin alpha Chains
  • Interleukin-17
  • Interleukins
  • Minor Histocompatibility Antigens
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Oligosaccharides
  • RORC protein, human
  • Receptors, CCR10
  • Receptors, CCR4
  • Sialyl Lewis X Antigen
  • alpha E integrins
  • Receptor, Interferon alpha-beta
  • Aminopeptidases
  • ERAP1 protein, human
  • interleukin-22