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 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. Synopsis: T‐cell infiltrates in muscle biopsies of patients with idiopathic inflammatory myopathies (IIM) have been described for decades. Using single‐cell sequencing, we show that muscle‐infiltrating T cells display tissue resident memory features and that they persist in muscle tissue over time.Muscle‐infiltrating T cells are characterized by an effector, regulatory, proliferating, or tissue resident memory (TRM) phenotype.Expanded T‐cell clones with effector (GRANZYME B) and tissue resident memory features (HOBIT, CXCR6) are identified in the muscle biopsies.Effector‐ and TRM clones persist in the muscle tissue after immunosuppressive treatmentA type 1 interferon signature is detected in T cells in the muscle tissue of patients with dermatomyositis and anti‐synthetase syndrome at early diagnosis. [ABSTRACT FROM AUTHOR]