Lnc-C/EBP? Modulates Differentiation of MDSCs Through Downregulating IL4i1 With C/EBP? LIP and WDR5.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b+Ly6ChiLy6G- monocytic MDSC (Mo-MDSC) and CD11b+Ly6Clow/negLy6G+ 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 lnc-C/EBP? may promote PMN-MDSC but impede differentiation of Mo-MDSCs in vitro and in vivo. We demonstrated that lnc-C/EBP? mediated differentiation of MDSCs was through downregulating multiple transcripts such as IL4il. Lnc-C/EBP? not only bound to C/EBP? isoform LIP to inhibit the activation of C/EBP? but also interacted with WDR5 to interrupt the enrichment of H3K4me3 mark on the promoter region of IL4i1. Data also imply that conserved homo lnc-C/EBP? has a similar function with mouse lnc-C/EBP?. Since MDSC subsets exert different suppressive function, lnc-C/EBP? may be acted as a potential therapeutic target for inflammatory and tumor-associated diseases.

SUBMITTER: Gao Y 

PROVIDER: S-EPMC6650770 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature