Targeting TLRs and the inflammasome in systemic sclerosis

Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterised by inflammation, vascular problems, cytokine dysregulation and ultimately fibrosis, which accounts for poor prognosis and eventual mortality. At present no curative treatments exist, hence there is an urgent need to better understand the aetiology and develop improved therapies accordingly. Although still widely debated, significant evidence points to upregulation of the innate immune response via the activity of Toll-like receptors (TLRs) and the NLRP3 inflammasome as the start points in a cascade of signaling events which drives excessive extracellular matrix protein production, causing fibrosis. Herein the recent breakthroughs which have implicated TLR signaling and the NLRP3 inflammasome in SSc and the novel therapeutic possibilities this introduces to the field will be discussed