title: Targeting defective Toll-like receptor-3 function and idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a disease of the lung parenchyma that is invariably fatal with a median survival of 2 - 3 years. Despite considerable progress in defining the natural history of the disease, many features of IPF pathogenesis remain poorly understood. Several recent studies have highlighted links between pattern recognition receptors of innate immunity termed 'Toll-like receptors' (TLRs) and the aberrant fibrogenesis that characterizes IPF.
  
  
  METHODS
  In this paper, we discuss the natural history of IPF and the identification of several distinct clinical phenotypes in recent years. TLRs are receptors that recognize pathogen- and/or danger-associated molecular patterns and promote an appropriate immune response. We describe in detail some of the recent works linking defective TLR3 function and an aggressive phenotype in IPF and explore the mechanisms and potential clinical implications of this initial observation.
  
  
  CONCLUSIONS
  We explore the potential role of TLRs in this setting. We discuss recent genetic studies and the implications for future research. We propose a model of dysregulated innate immune recognition and aberrant lung healing. The potential role of research in aiding the design of clinical trials and the evidence for targeting defective TLR3 function in IPF is presented.
authors.affiliation: University College Dublin, Conway Institute of Biomolecular and Biomedical Research, College of Life Sciences, School of Medicine and Medical Science , Belfield, Dublin , Ireland.
authors.forename: David N
authors.initials: DN
authors.lastname: O'Dwyer
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Armstrong
authors.forename: Minesh
authors.initials: M
authors.lastname: Kooblall
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D007113:Immunity, Innate; D058990:Molecular Targeted Therapy; D010641:Phenotype; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3
keywords: Toll-like receptors; idiopathic pulmonary fibrosis