The inflammatory milieu cells and cytokines

Idiopathic inflammatory myopathies (IIMs) are characterized by mononuclear inflammatory cell infiltrates in skeletal muscle with associated weakness and fatigue, although often the severity of inflammation does not correlate with clinical severity. Inflammation of other organs such as skin, lung, and gastrointestinal tract may also occur. IIMs are classified based on clinical, immunologic, and histopathologic features and include, but are not limited to, adult and juvenile dermatomyositis (DM and JDM, respectively), polymyositis (PM), and sporadic inclusion body myositis (IBM). Mononuclear cells are typically the major component of muscle inflammatory infiltrates in IIMs and include T lymphocytes (T cells), macrophages, dendritic cells (DCs), and B lymphocytes (B cells). Patterns of IIM inflammatory infiltrates include diffuse, endomysial, and perivascular. Endomysial infiltrates are composed primarily of T cells, with a high prevalence of CD8⁺ T cells, and to a lesser extent CD4⁺ T cells, DCs, and macrophages. These infiltrates typically surround muscle fibers that lack features of degeneration or necrosis. Perivascular infiltrates are composed mainly of CD4⁺ T cells and include macrophages, DCs, and B cells. The importance of B cells is increasingly becoming appreciated, and their involvement is likely to be critical in pathologic processes, especially related to autoantibody production and formation of ectopic lymphoid aggregates. Histopathologic features and phenotypic variability of inflammatory infiltrates, localization of infiltrates, presence of rimmed vacuoles, and involvement of microvasculature all contribute to defining IIM subsets. While we do not yet fully understand the pathological processes involved in IIMs, we are gaining information and clarity at a rapid pace. With advances in immunological detection, gene expression, protein biomarkers, and imaging of immune responses, our understanding of the molecules, pathways, and cells involved in pathogenesis continues to improve. We have only just started to understand the orchestrated life of T cells, B cells, macrophages, and DCs in myositis; many questions remain unanswered on how a system that is perturbed on a daily basis involves a large-scale but localized abnormal immune reaction.