The mushroom known as Reishi (Ganoderma lucidum) has been used as an herbal medicine for tumor treatment and immune system activation. Because its effects on the differentiation of effector T helper cells have not yet been fully understood, we investigated the effects of Reishi and those of its principal ingredient, beta-glucan, on the activation of dendritic cells and the differentiation of Th17 cells. Reishi extracts as well as purified beta-glucan (Curdran) activated DCs and caused them to produce large amounts of IL-23. beta-glucan also enhanced and sustained the transcription of IL-23p19. The MEK-ERK signaling pathway positively regulates IL-23p19 transcription in beta-glucan-stimulated DCs. In a mixed leukocyte reaction, Reishi-stimulated DCs preferentially induced Th17 cells. Furthermore, orally-administrated Reishi increased the percentages of Th17 cells and the transcription levels of antimicrobial peptides. Our results show that Reishi and p-glucan activate DCs to produce large amounts of IL-23, which induces Th17 differentiation both in vitro and in vivo. (C) 2012 Elsevier Inc. All rights reserved.