IL‐23 inhibits innate IFN‐γ secretion

Abstract

Most studies have concluded that interleukin‐23 (IL‐23) promotes IL‐17 secreting T cells. While some reports have also characterized IL‐23 as having redundant pro‐inflammatory effects with IL‐12, we have instead found that IL‐23 can regulate the innate immune response in a novel manner, by antagonizing IL‐12 induced secretion of interferon‐γ (IFN‐γ). Our recent data documents the rapid, innate production of IFN‐γ from memory CD8 T cells, as well as NK cells, stimulated with IL‐12 and IL‐18. When splenocytes are cultured with IL‐23, IFN‐γ secretion in response to IL‐12 is dramatically reduced, as measured by ELISA and intracellular cytokine staining. The impact of IL‐23 is most prominent in CD8 T cells, but can also be seen in NK, NK‐T, and CD4 T cells. We also show that IL‐23 can regulate the induction of IFN‐γ by endogenously produced IL‐12 from Listeria monocytogenes (LM) infected macrophages. In vivo, LM infection induces higher serum IFN‐γ levels and a greater percentage of IFN‐γ + CD8 T cells in IL‐23p19 deficient mice as compared to wild‐type mice. We are currently investigating the mechanism by which IL‐23 inhibits IFN‐γ secretion, and if IL‐23 can inhibit other effector functions. Our data suggest that IL‐23 may be a key player in determining the responsiveness of lymphocytes to IL‐12 and their subsequent secretion of IFN‐γ.