Figure 3.

Basic role of TLRs in myositis: post tissue damage (eg, via infection or exercise), cells release DAMPs.

Notes: These DAMPs ligate to TLRs on infiltrating cells such as macrophages and plasmacytoid cells. The ligation ultimately results in the secretion of proinflammatory molecules into the microenvironment. IL-1 binds to its receptor, IL-1R, and exerts its downstream effects, which lead to capillary loss and hypoxia. The damage to the cells caused by the cytokine, in turn, produces more DAMPs that can bind to the TLR and induce further inflammation and increase chemokine release in the muscle fibers. Recent murine models of myositis have shown the importance of TLR8, MyD88, and NF-κB in the development of myositis.⁸⁴ Possible dysregulation of miRNA and long noncoding RNAs and altered inflammation resolution also contribute.

Abbreviations: DAMPs, damage-associated molecular patterns; ECM, extracellular matrix; FLS, fibroblast-like synoviocytes; IL, interleukin; miRNA, microRNA; MMPs, matrix metalloproteinases; NF-kB, nuclear factor kappa B; TLR, toll-like receptor; TNF-α, tumor necrosis factor-α.