title: Myeloid interferon-γ receptor deficiency does not affect atherosclerosis in LDLR(-/-) mice.
abstract: OBJECTIVE
  Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Interferon gamma (IFNγ) is an important immunomodulatory cytokine and a known pro-atherosclerotic mediator. However, cell-specific targeting of IFNγ or its signaling in atherosclerosis development has not been studied yet. As macrophages are important IFNγ targets, we here addressed the involvement of myeloid IFNγ signaling in murine atherosclerosis.
  
  
  METHODS
  Bone marrow was isolated from interferon gamma receptor 2 chain (IFNγR2) wildtype and myeloid IFNγR2 deficient mice and injected into lethally irradiated LDLR(-/-) mice. After recovery mice were put on a high fat diet for 10 weeks after which atherosclerotic lesion analysis was performed. In addition, the accompanying liver inflammation was assessed.
  
  
  RESULTS
  Even though absence of myeloid IFNγ signaling attenuated the myeloid IFNγ response, no significant differences in atherosclerotic lesion size or phenotype were found. Also, when examining the liver inflammatory state no effects of IFNγR2 deficiency could be observed.
  
  
  CONCLUSIONS
  Overall, our data argue against a role for myeloid IFNγR2 in atherosclerosis development. Since myeloid IFNγ signaling seems to be nonessential throughout atherogenesis, it is important to understand the mechanisms by which IFNγ acts in atherogenesis. In the future new studies should be performed considering other cell-specific targets.
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marieke C S
authors.initials: MC
authors.lastname: Boshuizen
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Neele
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: van der Velden
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marten A
authors.initials: MA
authors.lastname: Hoeksema
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Forman
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Werner
authors.initials: W
authors.lastname: Muller
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Bossche
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.dewinther@amc.uva.nl.
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006505:Hepatitis / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D017471:Receptors, Interferon; D011973:Receptors, LDL; D000096743:Interferon gamma Receptor
keywords: Atherosclerosis; Interferon gamma receptor; Macrophage; Mouse model