Frontiers in Immunology (Oct 2024)

A distinct immune landscape in anti-synthetase syndrome profiled by a single-cell genomic study

  • Jiayu Ding,
  • Jiayu Ding,
  • Jiayu Ding,
  • Jiayu Ding,
  • Yanmei Li,
  • Yanmei Li,
  • Zhiqin Wang,
  • Zhiqin Wang,
  • Zhiqin Wang,
  • Zhiqin Wang,
  • Feng Han,
  • Feng Han,
  • Ming Chen,
  • Ming Chen,
  • Jun Du,
  • Jun Du,
  • Tong Yang,
  • Tong Yang,
  • Mei Zhang,
  • Mei Zhang,
  • Yingai Wang,
  • Yingai Wang,
  • Jing Xu,
  • Gaoya Wang,
  • Gaoya Wang,
  • Yong Xu,
  • Yong Xu,
  • Xiuhua Wu,
  • Xiuhua Wu,
  • Jian Hao,
  • Jian Hao,
  • Xinlei Liu,
  • Xinlei Liu,
  • Guangxin Zhang,
  • Na Zhang,
  • Na Zhang,
  • Wenwen Sun,
  • Wenwen Sun,
  • Zhigang Cai,
  • Zhigang Cai,
  • Zhigang Cai,
  • Zhigang Cai,
  • Zhigang Cai,
  • Wei Wei,
  • Wei Wei

DOI
https://doi.org/10.3389/fimmu.2024.1436114
Journal volume & issue
Vol. 15

Abstract

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ObjectivesThe objective of this study was to profile the transcriptional profiles of peripheral blood mononuclear cells (PBMCs) and their immune repertoires affected by anti-synthetase syndrome (ASS) at the single-cell level.MethodsWe performed single-cell RNA sequencing (scRNA-seq) analysis of PBMCs and bulk RNA sequencing for patients with ASS (N=3) and patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM, N=3) along with healthy controls (HCs, N=4). As ASS and MDA5+ DM have similar organ involvements, MDA5+ DM was used as a disease control. The immune repertoire was constructed by reusing the same scRNA-seq datasets. Importantly, flow cytometry was performed to verify the results from the scRNA-seq analysis.ResultsAfter meticulous annotation of PBMCs, we noticed a significant decrease in the proportion of mucosal-associated invariant T (MAIT) cells in ASS patients compared to HCs, while there was a notable increase in the proportion of proliferative NKT cells. Compared with MDA5+ DM patients, in their PBMCs ASS patients presented substantial enrichment of interferon pathways, which were primarily mediated by IFN-II, and displayed a weak immune response. Furthermore, ASS patients exhibited more pronounced metabolic abnormalities, which may in turn affect oxidative phosphorylation pathways. Monocytes from ASS patients appear to play a crucial role as receptive signaling cells for the TNF pathway. Immunophenotyping analysis of PBMCs from ASS patients revealed an increasing trend for the clone type CQQSYSTPWTF.ConclusionUsing single-cell genomic datasets of ASS PBMCs, we revealed a distinctive profile in the immune system of individuals with ASS, compared to that with MDA5+ DM or healthy controls.

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