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单细胞测序揭示了银屑病关节炎中表达组织归巢受体的促炎滑膜 CD8 T 细胞的克隆扩增。

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis.

机构信息

Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.

Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.

出版信息

Nat Commun. 2020 Sep 21;11(1):4767. doi: 10.1038/s41467-020-18513-6.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc2d/7505844/d31d932b9407/41467_2020_18513_Fig1_HTML.jpg

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