title: Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
abstract: 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.
authors.affiliation: Department of Internal Medicine, The University of Iowa, Iowa City, IA, United States of America.
authors.forename: Sophie
authors.initials: S
authors.lastname: Joly
authors.affiliation: Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Rhea
authors.affiliation: Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America.
authors.forename: Paige
authors.initials: P
authors.lastname: Volk
authors.affiliation: Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America.
authors.forename: Jessica G
authors.initials: JG
authors.lastname: Moreland
authors.affiliation: Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America.
authors.forename: Martine
authors.initials: M
authors.lastname: Dunnwald
mesh_terms: D000818:Animals; D054441:Cell Migration Assays, Leukocyte; D002478:Cells, Cultured; D002633:Chemotaxis; D016207:Cytokines / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology*
chemical_list: D016207:Cytokines; C528250:IRF6 protein, mouse; D050835:Interferon Regulatory Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B