Single-cell profiling of muscle-infiltrating T cells in idiopathic inflammatory myopathies

EMBO Mol Med. 2023 Oct 11;15(10):e17240. doi: 10.15252/emmm.202217240. Epub 2023 Jul 31.

Abstract

Idiopathic inflammatory myopathies (IIM) are rare autoimmune systemic diseases characterized by muscle weakness and the presence of muscle-infiltrating T cells. IIM represent a clinical challenge due to heterogeneity of symptoms and variability of response to immunosuppressive treatment. Here, we performed in-depth single-cell sequencing on muscle-infiltrating T cells and peripheral blood memory T cells in six patients with recently diagnosed IIM. We identified tissue resident memory T-cell (TRM ) signatures including the expression of HOBIT, XCL1 and CXCR6 in the muscle biopsies of all patients with IIM. Clonally expanded T-cell clones were mainly found among cytotoxic and TRM implying their role in the disease pathogenesis. Finally, identical expanded T-cell clones persisting at follow-up in the muscle tissue of two patients suggest their involvement in disease chronicity. Our study reveals a muscle tissue resident memory T-cell signature in patients with IIM and a transcriptomic map to identify novel therapeutic targets in IIM.

Keywords: HOBIT; T-cell receptor; idiopathic inflammatory myopathies; muscle; tissue resident memory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases*
  • Humans
  • Muscles
  • Myositis* / diagnosis
  • Myositis* / therapy
  • T-Lymphocytes