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_RM) 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_RM 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.

中文翻译：

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特发性炎症性肌病中肌肉浸润 T 细胞的单细胞分析

特发性炎症性肌病 (IIM) 是一种罕见的自身免疫性全身性疾病，其特征是肌肉无力和存在肌肉浸润 T 细胞。由于症状的异质性和对免疫抑制治疗的反应的可变性，IIM 代表了临床挑战。在这里，我们对 6 名最近诊断为 IIM 的患者的肌肉浸润 T 细胞和外周血记忆 T 细胞进行了深入的单细胞测序。我们在所有 IIM 患者的肌肉活检中鉴定了组织驻留记忆 T 细胞 (TRM _{)特征，包括}HOBIT、XCL1和CXCR6的表达。克隆扩增的 T 细胞克隆主要发现于细胞毒性和 TRM 中，这_表明它们在疾病发病机制中的作用。最后，两名患者的肌肉组织中持续存在相同的扩增 T 细胞克隆，表明它们与疾病的慢性化有关。我们的研究揭示了 IIM 患者肌肉组织驻留记忆 T 细胞特征和转录组图谱，以确定 IIM 的新治疗靶点。