Glucan from Dictyophora rubrovolvata boosts immunity by regulating AKT-STAT1 pathway to induce dendritic cells maturation and T cells differentiation

Glucan from fruit body of Dictyophora rubrovolvata (DRP) exerts immunomodulation activity, but the mechanism is still elusive. The immunoregulatory effects of DRP were evaluated using cyclophosphamide (CTX)-induced immunosuppression in BALB/c mice. Furthermore, bone marrow dendritic cells were used to investigate the activated effect of DRP on immune cells in vitro. This study pointed out that DRP recuperated CTX-induced immunosuppression of BALB/c mice and activated dendritic cells (DCs) to increase the secretion of cytokines in vitro. RNA-sequencing?showed that DRP upregulated the C-type lectin receptor (CLR), AKT-STAT1, and Th17 cell differentiation pathways in DCs. Furthermore, western blot and immunofluorescence confirmed that DRP increased the phosphorylation of AKT and STAT1 and the nuclear translocation of STAT1. Intriguingly, flow cytometry showed that the activation of DCs by DRP was interrupted by Mincle (a CLR) and STAT1 inhibitor. Furthermore, co-cultured experiments demonstrated that DRP promoted na?ve CD4 + T cell differentiation to Th17 cells via the stimulation of DCs. Hence, this study implied that DRP regulated the AKT-STAT1 signaling pathway via Mincle in DCs to induce CD4 + T cell proliferation and differentiation, thereby ameliorating CTX-induced immunosuppression.