Modulates Differentiation of MDSCs Through Downregulating IL4i1 With C/EBPβ LIP and WDR5.

Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11bLy6CLy6G monocytic MDSC (Mo-MDSC) and CD11bLy6CLy6G polymorphonuclear MDSC (PMN-MDSC) with different immunosuppressive function. However, it is poorly understood the mechanism(s) to control differentiation of Mo-MDSCs and PMN-MDSCs. Here, we found that β may promote PMN-MDSC but impede differentiation of Mo-MDSCs and . We demonstrated that β mediated differentiation of MDSCs was through downregulating multiple transcripts such as IL4il. β not only bound to C/EBPβ isoform LIP to inhibit the activation of C/EBPβ but also interacted with WDR5 to interrupt the enrichment of H3K4me3 mark on the promoter region of IL4i1. Data also imply that conserved homo β has a similar function with mouse β. Since MDSC subsets exert different suppressive function, β may be acted as a potential therapeutic target for inflammatory and tumor-associated diseases.