title: Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
abstract: Toll-like Receptor 3 (TLR3) is a pathogen pattern recognition receptor that plays a key role in innate immunity. TLR3 signalling has numerous functions in liver, both in health and disease. Here we report that TLR3 is expressed by quiescent hepatic stellate cells (HSC) where it functions to induce transcription and secretion of functional interferons as well as a number of other cytokines and chemokines. Upon transdifferentiation into myofibroblasts, HSCs rapidly loose the ability to produce interferon gamma (IFNγ). Mechanistically, this gene silencing may be due to Polycomb complex mediated repression via methylation of histone H3 lysine 27. In contrast to wild type, quiescent HSC isolated from tlr3 knockout mice do not produce IFNγ in response to Poly(I∶C) treatment. Therefore, quiescent HSC may contribute to induction of the hepatic innate immune system in response to injury or infection.
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Wilson
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Jelena
authors.initials: J
authors.lastname: Mann
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Meagan
authors.initials: M
authors.lastname: Walsh
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Perrugoria
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Oakley
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wright
authors.affiliation: Experimental Therapy Unit, Laboratory of Oncology, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Brignole
authors.affiliation: Experimental Therapy Unit, Laboratory of Oncology, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Paolo
authors.affiliation: Experimental Therapy Unit, Laboratory of Oncology, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Perri
authors.affiliation: Experimental Therapy Unit, Laboratory of Oncology, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Mirco
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Mann
mesh_terms: D000818:Animals; D002453:Cell Cycle; D016207:Cytokines / Q000096:biosynthesis; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007372:Interferons / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D063146:Polycomb-Group Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D008024:Ligands; D063146:Polycomb-Group Proteins; C519703:TLR3 protein, mouse; C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3; D007372:Interferons