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

• Published in: EMBO molecular medicine Vol. 15; no. 10; p. e17240
• Main Authors: Argyriou, Alexandra, Horuluoglu, Begum, Galindo-Feria, Angeles Shunashy, Diaz-Boada, Juan Sebastian, Sijbranda, Merel, Notarnicola, Antonella, Dani, Lara, van Vollenhoven, Annika, Ramsköld, Daniel, Nennesmo, Inger, Dastmalchi, Maryam, Lundberg, Ingrid E, Diaz-Gallo, Lina-Marcela, Chemin, Karine
• Format: Journal Article
• Language: English
• Published: England EMBO Press 11-10-2023; John Wiley and Sons Inc; Springer Nature
• Subjects: Biopsy; Cloning; Cytotoxicity; Datasets; Disease; Flow cytometry; Gene expression; HOBIT; idiopathic inflammatory myopathies; Immunological memory; Inflammation; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Memory cells; muscle; Musculoskeletal system; Pathogenesis; Patients; Peripheral blood; Resource; Therapeutic targets; tissue resident memory T cells; Transcription factors; Transcriptomics; T‐cell receptor; T-cell receptor; idiopathic inflammatory myopathies; tissue resident memory T cells; HOBIT; muscle
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.15252/emmm.202217240

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 (T
) 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 T
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.