Although anti-IL-23p19 therapy reduces the expression of several proinflammatory cytokines, it does not significantly suppress the progression of atherosclerosis in ApoE<sup>-/-</sup> mice.
Our work uncovers the IL-23-IL-22 signaling as a regulator of atherosclerosis that restrains expansion of pro-atherogenic microbiota and argues for informed use of cytokine blockers to avoid cardiovascular side effects driven by microbiota and inflammation.
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.
Furthermore, we observed the serum concentrations of HMGB1, IL-17A, and IL-23 were significantly higher in the AS group than in the NCA group (P＜0.01, respectively), whereas the concentrations of serum IL-10 and TGF-β1 were significantly lower in the AS group than in the NCA group (P＜0.01, respectively).
Our data reinforce the potential role of the IL-23 as a critical regulatory molecule that bridges the innate and adaptive arms of the immune system in the complex mechanisms associated with the development of atherosclerosis.