Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.

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 t...

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Main Authors: Caroline L Wilson, Jelena Mann, Meagan Walsh, Maria J Perrugoria, Fiona Oakley, Matthew C Wright, Chiara Brignole, Daniela Di Paolo, Patrizia Perri, Mirco Ponzoni, Michael Karin, Derek A Mann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0083391
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author Caroline L Wilson
Jelena Mann
Meagan Walsh
Maria J Perrugoria
Fiona Oakley
Matthew C Wright
Chiara Brignole
Daniela Di Paolo
Patrizia Perri
Mirco Ponzoni
Michael Karin
Derek A Mann
author_facet Caroline L Wilson
Jelena Mann
Meagan Walsh
Maria J Perrugoria
Fiona Oakley
Matthew C Wright
Chiara Brignole
Daniela Di Paolo
Patrizia Perri
Mirco Ponzoni
Michael Karin
Derek A Mann
author_sort Caroline L Wilson
collection DOAJ
description 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.
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institution Kabale University
issn 1932-6203
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publishDate 2014-01-01
publisher Public Library of Science (PLoS)
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series PLoS ONE
spelling doaj-art-71f7d585cd604254ace52ba7bc53da0f2025-08-20T03:46:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8339110.1371/journal.pone.0083391Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.Caroline L WilsonJelena MannMeagan WalshMaria J PerrugoriaFiona OakleyMatthew C WrightChiara BrignoleDaniela Di PaoloPatrizia PerriMirco PonzoniMichael KarinDerek A MannToll-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.https://doi.org/10.1371/journal.pone.0083391
spellingShingle Caroline L Wilson
Jelena Mann
Meagan Walsh
Maria J Perrugoria
Fiona Oakley
Matthew C Wright
Chiara Brignole
Daniela Di Paolo
Patrizia Perri
Mirco Ponzoni
Michael Karin
Derek A Mann
Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
PLoS ONE
title Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
title_full Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
title_fullStr Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
title_full_unstemmed Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
title_short Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
title_sort quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via tlr3
url https://doi.org/10.1371/journal.pone.0083391
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