Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Engelbertsen, Daniel LU ; Depuydt, Marie A.C. ; Verwilligen, Robin A.F. ; Rattik, Sara LU ; Levinsohn, Erik ; Edsfeldt, Andreas LU orcid ; Kuperwaser, Felicia ; Jarolim, Petr and Lichtman, Andrew H. (2018) In Journal of the American Heart Association 7(8).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, IL-17, IL-23R, Lymphocyte, Th17
in
Journal of the American Heart Association
volume
7
issue
8
article number
e008257
publisher
Wiley-Blackwell
external identifiers
  • pmid:29618473
  • scopus:85045306731
ISSN
2047-9980
DOI
10.1161/JAHA.117.008257
language
English
LU publication?
yes
id
afafc91c-d3b3-4e96-9030-8ccae0c7310f
date added to LUP
2018-04-23 14:15:20
date last changed
2025-10-14 09:46:48
@article{afafc91c-d3b3-4e96-9030-8ccae0c7310f,
  abstract     = {{<p>Background--Interleukin-23 (IL-23) has been implicated in inflammatory and autoimmune diseases by skewing CD4<sup>+</sup> 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<sup>-/-</sup>Il23r<sup>eGFP/WT</sup> knock-in mice to identify IL-23R-expressing cells by flow cytometry and homozygous Ldlr<sup>-/-</sup>Il23r<sup>eGFP/eGFP</sup> (Ldlr<sup>-/-</sup> Il23r<sup>-/-</sup>) 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<sup>+</sup> cells of all CD45<sup>+</sup> 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<sup>-/-</sup> Il23r<sup>-/-</sup> compared with Ldlr<sup>-/-</sup>controls. However, Ldlr<sup>-/-</sup> and Ldlr<sup>-/-</sup>Il23r<sup>-/-</sup> mice had equivalent amounts of aortic sinus and descending aorta lesions. Adoptive transfer of IL-23R-deficient CD4+ T cells to lymphopenic Ldlr<sup>-/-</sup>Rag1<sup>-/-</sup> resulted in dramatically reduced IL-17-producing T cells but did not reduce atherosclerosis, compared with transfer of IL-23R-sufficient CD4<sup>+</sup> 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.</p>}},
  author       = {{Engelbertsen, Daniel and Depuydt, Marie A.C. and Verwilligen, Robin A.F. and Rattik, Sara and Levinsohn, Erik and Edsfeldt, Andreas and Kuperwaser, Felicia and Jarolim, Petr and Lichtman, Andrew H.}},
  issn         = {{2047-9980}},
  keywords     = {{Atherosclerosis; IL-17; IL-23R; Lymphocyte; Th17}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{8}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{IL-23R deficiency does not impact atherosclerotic plaque development in mice}},
  url          = {{http://dx.doi.org/10.1161/JAHA.117.008257}},
  doi          = {{10.1161/JAHA.117.008257}},
  volume       = {{7}},
  year         = {{2018}},
}