title: Innate Immunity in Systemic Sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a heterogeneous autoimmune disease which has defined three hallmarks: Small vessel vasculopathy, production of autoantibodies and fibroblast dysfunction. The exact aetiology of the disease remains unknown, due to the complex nature of the cellular signalling pathways involved. However, there is strong and consistent evidence that the innate system, in particular toll-like receptor signalling, is contributing to the progression and perhaps onset of systemic sclerosis. In light of this evidence, this review examines the role of innate immunity in systemic sclerosis and where appropriate suggests avenues for therapeutic modulation in SSc.
  
  
  RESULTS
  Multiple lines of evidence suggest that Toll-like receptors (TLRs) are dysregulated and emerging evidence suggests that many endogenous ligands are also elevated in the disease leading to 'sterile inflammation' and ultimately the induction of fibrosis. Currently, no effective therapy exists and exploiting the innate immune system perturbation may be one possible avenue. Innate immune dysregulation is key in SSc pathogenesis and may represent a novel target.
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Ellison Building, Newcastle Upon Tyne, NE2 8ST, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dowson
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Ellison Building, Newcastle Upon Tyne, NE2 8ST, UK.
authors.forename: Nathan
authors.initials: N
authors.lastname: Simpson
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Ellison Building, Newcastle Upon Tyne, NE2 8ST, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Duffy
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Ellison Building, Newcastle Upon Tyne, NE2 8ST, UK. steven.oreilly@northumbria.ac.uk.
authors.forename: Steven
authors.initials: S
authors.lastname: O'Reilly
mesh_terms: D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D058847:Inflammasomes; D051193:Toll-Like Receptors; D003165:Complement System Proteins
keywords: Autoimmune disease; SSc; Scleroderma; Systemic sclerosis