AbstractThe immune system plays a crucial role in protecting the body from harmful bacterial, viral infections and vital for cancer suppression. Dendritic cells (DCs) are indispensable mediators that facilitate the connection between innate and acquired immunity via antigen presentation and cytokine production. One of the major intestinal microbial metabolites of green tea polyphenols, 5-(3′,5′-dihydroxyphenyl)-γ-valerolactone (EGC-M5), enhances T cell activity. However, the detailed underlying mechanisms remain unknown. Here, we revealed that the oral administration of EGC-M5 increases and activates plasma cytoid dendritic cells (pDCs) in the spleen without causing changes in body weight. Consistent with these findings, administration of EGC-M5 increased the gene expression of interleukin-12 in the spleen. Oral administration of EGC-M5 significantly increased type I Interferon (IFN) and IL-6 levels, which are involved in vaccine-induced antibody production. Ex vivo experiments showed that EGC-M5 treatment did not directly enhance pDC differentiation. In conclusion, EGC-M5 indirectly increased pDC levels in vivo, accompanied by an increase in the expression of pDC activation markers and the gene expression of interleukin-12, type I IFN and IL-6 in the spleen.Graphical abstract