Review Article

Role of Myokines in Myositis Pathogenesis and Their Potential to be New Therapeutic Targets in Idiopathic Inflammatory Myopathies

Figure 1

Schematic representation of myokines released in myositis. Skeletal muscle inflammation is induced by invading immune cells (thin dark green arrows): macrophages, T-cells (CD4 + T-cells, CD8 + T-cells), B cells which release proinflammatory cytokines (IL: interleukin; IFN: interferon; TNF: tumour necrosis factor). Most important cytokines related to myokines releasing are IL-1α/β, IL17, TNF-α, and INF-γ. In response to inflammation, MHC class I is overexpressed on the sarcolemma, contributing to muscle injury. Moreover, MHC I activates ER stress response and inflammasome activation. Immunoproteasome and endoplasmic reticulum (ER) stress contribute, in turn, to MHC I overexpression (thin green arrows). Under these conditions, muscle cells secrete myokines (thick green arrows), such as interleukins—IL-6, IL-15, IL-18; chemokines—CCL2, CCL3, CCL4, CCL5, CCL9, CCL20, CXCL8, CXCL9, CXCL10 (the most important in red); myostatin, follistatin, osteonectin, decorin (probably present, but uninvestigated in myositis), and insulin-like 6 (Insl6). Myokines, in turn, attract inflammatory cells, maintaining, to a certain extent, inflammation (thick blue arrows).