Recent advances in immunological mechanisms and murine disease models of idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are a group of autoimmune muscle disorders characterized by muscle weakness caused by muscle tissue inflammation, as well as lung and skin symptoms. Their pathophysiology and exacerbation are primarily associated with the tissue infiltration of immune cells, such as T cells and macrophages, revealing a strong connection with the immune system. Based on the clinical and pathological features of IIMs, polymyositis, which is characterized by CD8 T-cell infiltration around muscle fibers, and dermatomyositis, which is characterized by CD4 T-cell infiltration with complement infiltration around blood vessels, along with distinctive skin symptoms, have been traditionally distinguished. However, recent classifications based on autoantibodies and gene expression have proposed new categories, such as antisynthetase syndrome, clinical amyopathic dermatomyositis, immune-mediated necrotizing myopathy, and inclusion body myositis, resulting in the concept of IIM as a spectrum of diseases including these subtypes. Furthermore, advancements in next-generation sequencing have analyzed single-cell RNA sequencing and spatial transcriptomics using human patient samples, demonstrating the detailed characteristics of immune cell subsets, contributions of new immune cells, and interactions with effector cells in each disease subtype. A variety of IIM mouse models have been developed by activating the immune system through different methods, reflecting distinct myositis classifications within IIM. Recently, polymyositis models have used a humanized immune system, enabling the evaluation of therapeutics across species. This review provides an overview of the latest insights into the immunopathology of IIM and myositis models, reflecting various subtypes, advancing nonbiased and in-depth understanding using omics technologies.