Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.

Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2...

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Main Authors: Sophie Joly, Lindsey Rhea, Paige Volk, Jessica G Moreland, Martine Dunnwald
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4817988?pdf=render
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author Sophie Joly
Lindsey Rhea
Paige Volk
Jessica G Moreland
Martine Dunnwald
author_facet Sophie Joly
Lindsey Rhea
Paige Volk
Jessica G Moreland
Martine Dunnwald
author_sort Sophie Joly
collection DOAJ
description Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.
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spelling doaj.art-34d21b2d616a468fa270a247bd9ee0da2022-12-21T20:26:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01114e015238510.1371/journal.pone.0152385Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.Sophie JolyLindsey RheaPaige VolkJessica G MorelandMartine DunnwaldInterferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.http://europepmc.org/articles/PMC4817988?pdf=render
spellingShingle Sophie Joly
Lindsey Rhea
Paige Volk
Jessica G Moreland
Martine Dunnwald
Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
PLoS ONE
title Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
title_full Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
title_fullStr Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
title_full_unstemmed Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
title_short Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
title_sort interferon regulatory factor 6 has a protective role in the host response to endotoxic shock
url http://europepmc.org/articles/PMC4817988?pdf=render
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