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

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^-/-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% 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.