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Quiescent Hepatic Stellate Cells Functionally Contribute to the Hepatic Innate Immune Response via TLR3

Lookup NU author(s): Dr Caroline WilsonORCiD, Professor Jelena Mann, Dr Meagan Walsh, Professor Fiona OakleyORCiD, Professor Matthew Wright, Dr Daniela Di Paolo, Professor Derek Mann

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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 (IFN gamma). 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 IFN gamma 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.

Publication metadata

Author(s): Wilson CL, Mann J, Walsh M, Perrugoria MJ, Oakley F, Wright MC, Brignole C, Di Paolo D, Perri P, Ponzoni M, Karin M, Mann DA

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2014

Volume: 9

Issue: 1

Print publication date: 08/01/2014

Online publication date: 08/01/2014

Acceptance date: 04/11/2013

Date deposited: 28/03/2014

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0083391

DOI: 10.1371/journal.pone.0083391

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