Aim: To investigate the role of cytokines (IL-23, IL-2 and IL-15) in the production and regulation of IL-17 and IFN-gamma via the induction of normal human peripheral blood mononuclear cells (PBMCs) and CD4(+) T cells.
Methods: PBMCs or CD4(+) T cells from normal human blood were cultured with IL-23, IL-2 or IL-15 in the presence or absence of IL-23. The level of IL-17 and IFN-gamma in the culture supernatants was assessed by ELISA. The frequency of IL-17 and IFN-gamma produced cells was detected by ELISPOT.
Results: IL-23 induced PBMCs to produce IL-17 and IFN-gamma. IL-2 and IL-15 induced the production of IL-17 and IFN-gamma in a dose dependent manner by PBMCs. Similar results were confirmed by ELISPOT assay. The addition of Th2 cytokines (IL-4 and IL-10) or anti-IL-12Rbeta1 mAbs resulted in the inhibition of IL-17 and IFN-gamma production induced by IL-23. Further study suggested that IL-23, IL-2 and IL-15 directly induced the production of IL-17 and IFN-gamma by purified CD4(+) T cells.
Conclusion: IL-23, IL-2 and IL-15 can directly induce CD4(+) T cells to produce IL-17 and IFN-gamma. The production of IL-17 and IFN-gamma induced by IL-23 can be inhibited by Th2 cytokines and anti-IL-12Rbeta1 mAbs. The finding of our research may provide some new targets for the study of mechanism and treatment of IL-17-mediated autoimmune diseases.