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

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 pe...

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Bibliographic Details
Published in:EMBO molecular medicine 2023-10, Vol.15 (10), p.e17240-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: Article
Language:English
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
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Summary: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.
ISSN:1757-4676
1757-4684
1757-4684
DOI:10.15252/emmm.202217240