Differentiation-inducing factor-1 inhibits dendritic cell function by attenuating toll-like receptor 4 and phospho-nuclear factor-κB signaling in vitro

Dendritic cells (DCs) play a crucial role in initiating immune responses by presenting antigens to naïve T cells. Differentiation-inducing factor (DIF)-1, a signaling molecule that induces stalk cell differentiation in the cellular slime mold Dictyostelium discoideum, has limited known effects on murine bone marrow-derived DCs. In this study, DIF-1 attenuated both the phenotypic and functional activation of murine DCs upon stimulation with lipopolysaccharide (LPS). Specifically, DIF-1 downregulated the expression of major histocompatibility complex class II molecules and the co-stimulatory molecule CD86 in LPS-stimulated DCs. Moreover, DIF-1-treated DCs exhibited less-efficient stimulation of naïve allogeneic T-cell proliferation and reduced production of interleukin-12 and tumor necrosis factor-α. Additionally, DIF-1 inhibited the toll-like receptor 4-related and phospho-nuclear factor (NF)-κB signaling pathways. These findings provide novel insights into the immunopharmacology of DIF-1 and suggest a potential therapeutic approach for modulating DC function in immune-related therapies.