Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.
Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Nat Commun. 2020 Sep 21;11(1):4767. doi: 10.1038/s41467-020-18513-6.
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.
银屑病关节炎(PsA)是一种病因不明的使人衰弱的免疫介导性炎症性关节炎,通常影响患有银屑病的患者。在这里,我们使用互补的单细胞方法来研究银屑病关节炎关节中的白细胞。质谱流式细胞术显示,与外周血相比,银屑病关节炎患者关节中的记忆性 CD8 T 细胞扩增了 3 倍。同时,基于液滴的和基于平板的 T 细胞受体 alpha 和 beta 链序列的单细胞 RNA 测序显示,关节内存在明显的 CD8 T 细胞克隆扩增。转录组分析发现这些扩增的滑膜 CD8 T 细胞表达循环、激活、组织归巢和组织驻留标志物。患者之间的 T 细胞受体序列比较表明存在克隆收敛。最后,趋化因子受体 CXCR3 在扩增的滑膜 CD8 T 细胞中上调,而两个 CXCR3 配体 CXCL9 和 CXCL10 在银屑病关节炎滑膜液中升高。因此,我们的数据为银屑病关节炎的细胞免疫景观提供了定量的分子见解。