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

Daniel Engelbertsen, Marie A.C. Depuydt, Robin A.F. Verwilligen, Sara Rattik, Erik Levinsohn, Andreas Edsfeldt, Felicia Kuperwaser, Petr Jarolim, Andrew H. Lichtman

Research output: Contribution to journalArticlepeer-review

9 Citations (SciVal)

Abstract

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.

Original languageEnglish
Article numbere008257
JournalJournal of the American Heart Association
Volume7
Issue number8
DOIs
Publication statusPublished - 2018 Apr 17

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems

Keywords

  • Atherosclerosis
  • IL-17
  • IL-23R
  • Lymphocyte
  • Th17

Fingerprint

Dive into the research topics of 'IL-23R deficiency does not impact atherosclerotic plaque development in mice'. Together they form a unique fingerprint.

Cite this