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Nat Commun ; 11(1): 4767, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958743

RESUMO

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis.


Assuntos
Artrite Psoriásica/imunologia , Linfócitos T CD8-Positivos/imunologia , Seleção Clonal Mediada por Antígeno , Receptores de Retorno de Linfócitos/metabolismo , Líquido Sinovial/imunologia , Artrite Psoriásica/sangue , Linfócitos T CD8-Positivos/metabolismo , Perfilação da Expressão Gênica , Humanos , Memória Imunológica , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Quimiocinas/metabolismo , Receptores de Retorno de Linfócitos/genética , Análise de Célula Única , Membrana Sinovial/imunologia
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