Single cell RNA sequencing sheds light on infiltrating T cells in idiopathic inflammatory myopathies

Abstract

Idiopathic inflammatory myopathies (IIM), also referred to as "myositis," are a group of heterogeneous autoimmune disorders characterised by muscle weakness, atrophy and progressive reduced mobility (Lundberg et al, 2021). IIM represent a significant health burden in adult populations, affecting individuals at a mean age of 50 with an estimated prevalence of 2.9-34 per 100,000 (Dobloug et al, 2015; Svensson et al, 2017). IIM encompass several subtypes including dermatomyositis, immune-mediated necrotising myopathy, inclusion-body myositis, antisynthetase syndrome and polymyositis, which are characterised by specific clinical features, histopathological findings and autoantibody status (Pinal-Fernandez et al, 2020).

Figure 1. Single cell RNA sequencing of peripheral and infiltrating T cells in myositis

(A) Argyriou et al (2023) recruited seven patients with inflammatory myopathies obtaining skeletal muscle biopsies and peripheral blood (PB) mononucleated cells. T‐cell muscle infiltration was confirmed with CD3 immunostaining. Two patients underwent tissue biopsy and PB mononucleated cells isolation after treatment. (B) Tissue infiltrating and PB T‐cells were isolated and sorted using FACS. Smart‐seq2/3 allowed transcriptome sequencing of 1,402 cells in biopsies and 1,417 cells from PB. Unbiased clustering and Uniform Manifold Approximation and Projection (UMAP) embedding identified central memory (CM) cells, CZMB⁺ effector memory (EM) cells, HOBIT⁺ tissue resident memory (TRM), EGR‐1⁺ TRM cells, HLA‐DR⁺ TRM cells, KLRB1⁺ EM cells, CD69⁺ EM cells, CXCL 13⁺ TRM cells, Regulatory T cells (Tregs) and proliferating T cells. (C) The key findings included identification of muscle resident memory T cells, clonal expansion of tissue resident and PB T cells and persistence of the identical clones in blood and tissue after immunosuppressive therapy (Figure was created using Biorender).