Journal
CURRENT OPINION IN RHEUMATOLOGY
Volume 32, Issue 6, Pages 515-522Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/BOR.0000000000000748
Keywords
autophagy; denervation; endoplasmic-reticulum stress; idiopathic inflammatory myopathies; mitochondria; neuromuscular junction
Categories
Ask authors/readers for more resources
Purpose of review This review encompasses the main novelties regarding nonimmune mechanisms implicated in the pathogenesis of idiopathic inflammatory myopathies (IIM). Recent findings In recent years, growing data support a role for endoplasmic-reticulum (ER) stress as a propagator of muscular damage, together with the release of interferon type I and reactive oxygen species in hypoxemic muscle fibers. Other studies evaluating the relationship between autophagy and Toll-like receptors (TLRs) in IIM subtypes have shown increased TLR3 and TLR4 expression in fibers of IIM patients and colocalization with LC3, an autophagy marker, submitting autophagy as a likely player in IIM pathogenesis. Most novel evidences concern the potential role of denervation of the neuromuscular junction in IIM, possibly connected to hyperexpression of MHC-I, and trafficking of extracellular vesicles, which may represent a connection between nonimmune and immune-mediated mechanisms of muscle inflammation and damage. Nonimmune mechanisms contribute to the pathogenesis of IIM, likely cooperating with immune-mediated inflammation. Consistent data were released for ER stress, autophagy, mitochondrial dysfunction and hypoxia; in addition to, neuromuscular denervation and extracellular vesicles have been proposed as thoughtful links between muscle inflammation, damage and atrophy. Further understanding of nonimmune abnormalities and potential reversible pathways is needed to improve the management of IIM.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available