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IL-23R deficiency does not impact atherosclerotic plaque development in mice

Author:
  • Daniel Engelbertsen
  • Marie A.C. Depuydt
  • Robin A.F. Verwilligen
  • Sara Rattik
  • Erik Levinsohn
  • Andreas Edsfeldt
  • Felicia Kuperwaser
  • Petr Jarolim
  • Andrew H. Lichtman
Publishing year: 2018-04-17
Language: English
Publication/Series: Journal of the American Heart Association
Volume: 7
Issue: 8
Document type: Journal article
Publisher: Wiley-Blackwell

Abstract english

Background--Interleukin-23 (IL-23) has been implicated in inflammatory and autoimmune diseases by skewing CD4+ T helper cells towards a pathogenic Th17 phenotype. In this study we investigated the presence of IL-23 receptor (IL-23R)-expressing cells in the atherosclerotic aorta and evaluated the effect of IL-23R deficiency on atherosclerosis development in mice. Methods and Results--We used heterozygous Ldlr-/-Il23reGFP/WT knock-in mice to identify IL-23R-expressing cells by flow cytometry and homozygous Ldlr-/-Il23reGFP/eGFP (Ldlr-/- Il23r-/-) mice to investigate the effect of lack of IL-23R in atherosclerosis. We demonstrate the presence of relatively rare IL-23R-expressing cells in lymphoid tissue and aorta (≈0.1-1% IL23R+ cells of all CD45+ leukocytes). After 10 weeks on a high-fat diet, production of IL-17, but not interferon-c, by CD4+ T cells and other lymphocytes was reduced in Ldlr-/- Il23r-/- compared with Ldlr-/-controls. However, Ldlr-/- and Ldlr-/-Il23r-/- mice had equivalent amounts of aortic sinus and descending aorta lesions. Adoptive transfer of IL-23R-deficient CD4+ T cells to lymphopenic Ldlr-/-Rag1-/- resulted in dramatically reduced IL-17-producing T cells but did not reduce atherosclerosis, compared with transfer of IL-23R-sufficient CD4+ T cells. Conclusions--These data demonstrate that loss of IL-23R does not affect development of experimental atherosclerosis in LDLrdeficient mice, despite a role for IL-23 in differentiation of IL-17-producing T cells.

Keywords

  • Cardiac and Cardiovascular Systems
  • Atherosclerosis
  • IL-17
  • IL-23R
  • Lymphocyte
  • Th17

Other

Published
  • Cardiovascular Research - Immunity and Athersosclerosis
  • ISSN: 2047-9980

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