Glucans from Lentinus edodes Inhibit Myeloid-Derived Suppressor Cell-Induced Regulatory T Cells via the TLR4-TAK1-JNK Signaling Pathway to Scavenge Reactive Oxygen Species.

A purified polysaccharide, named LENP-1, was prepared from Lentinus edodes and characterized. Structural analysis revealed that this polysaccharide was a (1 → 4)-glucan with a branched structure at the O-6 position via side chains of single α-d-glucopyranose (t-Glcp) residues. This polysaccharide did not inhibit the proliferation of Myeloid-Derived Suppressor Cells (MDSCs) but significantly weakened the inhibitory effect of MDSCs on T cell proliferation and reduced the proportion of regulatory T cells (Tregs). LENP-1 could significantly upregulate the levels of MyD88, TAK1, JNK, and c-Jun in MSC-2 cells, while both the ratio of NADP+/NADPH and the level of reactive oxygen species (ROS) were significantly downregulated. After blocking JNK or Toll-like receptor 4 (TLR4), the above effects of LENP-1 disappeared. In conclusion, LENP-1 could reduce the level of ROS in MDSCs, thereby decreasing the generation of Tregs. This effect is related to the TLR4-MyD88-TAK1-JNK-c-JUN-ROS signaling pathway.