title: Toll-like receptors in the pathogenesis of pulmonary fibrosis.
abstract: Pulmonary fibrosis (PF) constitutes the end stage of a broad range of heterogeneous interstitial lung diseases, characterized by the destruction of the pulmonary parenchyma, deposition of extracellular matrix and dramatic changes in the phenotype of both fibroblasts and alveolar epithelial cells. More than 200 causes of pulmonary fibrosis have been identified so far, yet the most common form is idiopathic pulmonary fibrosis (IPF). IPF is a lethal lung disorder of unknown etiology with a gradually increasing worldwide incidence and a median survival of 3-5 years from the time of diagnosis. Despite intense research efforts, the pathogenesis remains elusive and no effective treatment is available. Accumulating body of evidence suggests an abnormal wound healing response followed by extracellular matrix deposition, destruction of lung architecture, ultimately leading to respiratory failure. The contribution of immune system in lung fibrogenesis had been largely underscored due to the absence of response to immunosuppressive agents; however, the premise that lung fibrosis has an immunologic background has been recently revived. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs), which link innate and adaptive immune response and regulate wound healing. TLRs promote tissue repair or fibrosis in many disease settings including lung fibrosis, albeit with profound differences depending on the cellular microenvironment. This review summarizes the current state of knowledge regarding the mechanistic implications between TLRs and lung fibrosis and highlights the therapeutic potential of targeting TLR signaling at the ligand or receptor level.
authors.affiliation: Academic Department of Pneumonology, Hospital for Diseases of the Chest, "Sotiria", Medical School, University of Athens, Messogion Avenue 152, Athens 11527, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Karampitsakos
authors.affiliation: Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, P.O. Box 208057 New Haven, CT, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Woolard
authors.affiliation: Academic Department of Pneumonology, Hospital for Diseases of the Chest, "Sotiria", Medical School, University of Athens, Messogion Avenue 152, Athens 11527, Greece.
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros
authors.affiliation: Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, P.O. Box 208057 New Haven, CT, USA. Electronic address: argyrios.tzouvelekis@yale.edu.
authors.forename: Argyris
authors.initials: A
authors.lastname: Tzouvelekis
mesh_terms: D000818:Animals; D006801:Humans; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D051193:Toll-Like Receptors
keywords: Idiopathic Pulmonary Fibrosis; Immune response; Lung fibrosis; Toll like receptors; Wound healing