Cordycepin Suppresses MHC-restricted Antigen Presentation and Leads to Down-regulation of Inflammatory Responses in Antigen Presenting Cells

Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of cordycepin on the antigen-presenting function of antigen-presenting cells (APCs). Dendritic cells (DCs) were cultured in the presence of cordycepin and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through RT-PCR and Western blot analysis. Cordycepin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of cordycepin was also confirmed using mice that had been injected with cordycepin followed by soluble OVA. Furthermore, cordycepin suppressed the mRNA and protein levels of iNOS, COX-2, pro-inflammatory cytokines in a concentration-dependent manner. These results provide an understanding of the mechanism of the T cell response-regulating activity of cordycepin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.