Particulate β-glucan regulates the immunosuppression of granulocytic myeloid-derived suppressor cells by inhibiting NFIA expression

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells which comprise two subsets: granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). MDSCs involve in tumor-associated immune suppression by remarkably blocking effector T-cell activation and inducing expansion of regulatory T cells in the tumor microenvironment. The treatment that alters the suppression of MDSCs can effectively facilitate the antitumor immune responses. Recently, we showed that the whole β-glucan particles (WGPs) are capable of altering the suppression of MDSCs. However, the regulatory mechanism of MDSCs by WGP remains unknown. In this study, we found that the expression of nuclear factor I-A (NFIA), an integral transcriptional component of myeloid differentiation and lineage commitment, was inhibited by WGP in G-MDSCs. The effect of WGP on expression of NFIA was the c-jun molecule dependent via Dectin-1 pathway in vitro. Moreover, NFIA knockdown could alter the suppressive function of G-MDSCs, promote the antitumor immune responses and delay the tumor progression in tumor-bearing mice. Taken together, our results demonstrate a critical role of NFIA during WGP regulating the immunosuppression of G-MDSCs, with potential implications as an antitumor immune therapeutic approach.