IL-23R Deficiency Does Not Impact Atherosclerotic Plaque Development in Mice

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.

We used heterozygous LdlrIl23r^WT knock-in mice to identify IL-23R-expressing cells by flow cytometry and homozygous LdlrIl23r^eGFP (LdlrIl23r ) 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-γ, by CD4⁺ T cells and other lymphocytes was reduced in LdlrIl23r compared with Ldlr controls. However, Ldlr and LdlrIl23r mice had equivalent amounts of aortic sinus and descending aorta lesions. Adoptive transfer of IL-23R-deficient CD4⁺ T cells to lymphopenic LdlrRag1 resulted in dramatically reduced IL-17-producing T cells but did not reduce atherosclerosis, compared with transfer of IL-23R-sufficient CD4⁺ T cells.

These data demonstrate that loss of IL-23R does not affect development of experimental atherosclerosis in LDLr-deficient mice, despite a role for IL-23 in differentiation of IL-17-producing T cells.