Immunoregulation in Idiopathic Inflammatory Myopathies: From Dendritic Cells to Immature Regenerating Muscle Cells

Abstract

Idiopathic inflammatory myopathies (IIM) are a group of chronic muscle disorders of unknown origin that lead to muscle destruction. The original classification of IIM proposed by Bohan and Peter in 1975 including polymyositis (PM) and dermatomyositis (DM) was recently revised with the development of histopathological approaches and the discovery of myositis-specific and myositis-associated antibodies that led to the characterization of new entities. In addition to PM and adult and juvenile DM, these novel classifications distinguish inclusion-body myositis (IBM), immune-mediated necrotizing myopathy, overlap myositis, and cancer-associated myositis1,2. While distinct immunopathogenic mechanisms may occur in each subset of myositis, all IIM share a common inflammatory background associated with clinical, histological, and serological overlap. Several molecular pathways, such as adaptive and innate immune responses, autoimmunity, and nonimmune mechanisms, could influence the pathogenesis of IIM. However, the exact contribution of each one in the development of distinct phenotypes remains unclear. In this issue of The Journal , Gendek-Kubiak and Gendek highlight the contribution of dendritic cells (DC)3. We summarize here recent insights in myositis immunoregulation from DC that are central in the development of adaptive and innate response to nonimmune mechanisms. ### Dendritic cells DC are crucial for the development of adaptive and innate immune responses. DC, subdivided into myeloid DC (mDC) and plasmacytoid DC (pDC), are present in lymphatic and blood systems and peripheral organs. They are equipped with a range of pattern-recognition receptors (PRR) and serve as sentinels of the immune system. Their activation after stimulation of PRR, such as Toll-like receptors (TLR) or C-type lectin receptors (CLR), by microbial components and/or endogenous ligands leads to their maturation and the development of an effector T cell immune response. In muscle biopsies from IIM, both myeloid and plasmacytoid DC have been detected with differences according to IIM subtypes. The DC … Address correspondence to Dr. A. Tournadre, Department of Rheumatology, Gabriel Montpied Hospital, CHU Clermont-Ferrand, 58 rue Montalembert BP69, 63003 Clermont-Ferrand Cedex 1, France. E-mail: atournadre{at}chu-clermontferrand.fr