Open AccessIL ‐23R Deficiency Does Not Impact Atherosclerotic Plaque Development in Mice
Author(s) -
Engelbertsen Daniel,
Depuydt Marie A. C.,
Verwilligen Robin A. F.,
Rattik Sara,
Levinsohn Erik,
Edsfeldt Andreas,
Kuperwaser Felicia,
Jarolim Petr,
Lichtman Andrew H.
Publication year - 2018
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.008257
Subject(s) - ldl receptor , medicine , adoptive cell transfer , flow cytometry , interleukin 17 , immunology , immune system , inflammation , t cell , lipoprotein , cholesterol
Background Interleukin‐23 ( IL ‐23) has been implicated in inflammatory and autoimmune diseases by skewing CD 4 + 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 −/− Il23r eGFP/ WT knock‐in mice to identify IL ‐23R‐expressing cells by flow cytometry and homozygous Ldlr −/− Il23r eGFP/ 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% IL 23R + cells of all CD 45 + leukocytes). After 10 weeks on a high‐fat diet, production of IL ‐17, but not interferon‐γ, by CD 4 + 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 CD 4 + 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 CD 4 + T cells. Conclusions These data demonstrate that loss of IL ‐23R does not affect development of experimental atherosclerosis in LDL r‐deficient mice, despite a role for IL ‐23 in differentiation of IL ‐17‐producing T cells.