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

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 knock-in mice to identify IL-23R-expressing cells by flow cytometry and homozygous ( ) 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 compared with controls. However, and mice had equivalent amounts of aortic sinus and descending aorta lesions. Adoptive transfer of IL-23R-deficient CD4 T cells to lymphopenic 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 LDLr-deficient mice, despite a role for IL-23 in differentiation of IL-17-producing T cells.