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Andreas Edsfeltdt

Andreas Edsfeldt

Associate professor

Andreas Edsfeltdt

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

Summary, in 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.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis
  • EXODIAB: Excellence of Diabetes Research in Sweden

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

Topic

  • Cardiac and Cardiovascular Systems

Keywords

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

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 2047-9980