Pathogenesis of myositis: Lessons learned from animal studies

Recent studies have continued to clarify the pathogenic mechanisms responsible for muscle damage and weakness in inflammatory myopathies. Traditionally, adaptive immune mechanisms such as cell mediated (cytotoxic) and humoral (autoantibodies and complement) components have been implicated in the pathogenesis of polymyositis/inclusion body myositis and dermatomyositis, respectively. However, recent studies have shown a significant overlap of immune components in these disorders. Likewise, studies have provided evidence not only for adaptive immune pathogenic mechanisms but also for innate immune, such as the TLR-NF-κB signaling, and non-immune mechanisms, such as endoplasmic reticulum stress response, autophagy, metabolic deficits in ATP generating pathways and hypoxia. These recent studies indicate that the muscle fiber damage and weakness in myositis may not be solely mediated by an adaptive immune attack (e.g., autoreactive CTLs or autoantibodies) but also mediated through innate immune and metabolic mechanisms. In this review, we have briefly outlined the current developments in immune (adaptive, innate) and non-immune components of disease pathogenesis in inflammatory myopathies.