AUTHOR=Gao Yunhuan , Shang Wencong , Zhang Dan , Zhang Shiwu , Zhang Xipeng , Zhang Yuan , Yang Rongcun 

TITLE=Lnc-C/EBPβ Modulates Differentiation of MDSCs Through Downregulating IL4i1 With C/EBPβ LIP and WDR5

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01661

DOI=10.3389/fimmu.2019.01661

ISSN=1664-3224

ABSTRACT=<p>Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b<sup>+</sup>Ly6C<sup>hi</sup>Ly6G<sup>−</sup> monocytic MDSC (Mo-MDSC) and CD11b<sup>+</sup>Ly6C<sup>low/neg</sup>Ly6G<sup>+</sup> 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 <italic>lnc-C/EBP</italic>β may promote PMN-MDSC but impede differentiation of Mo-MDSCs <italic>in vitro</italic> and <italic>in vivo</italic>. We demonstrated that <italic>lnc-C/EBP</italic>β mediated differentiation of MDSCs was through downregulating multiple transcripts such as IL4il. <italic>Lnc-C/EBP</italic>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 <italic>lnc-C/EBP</italic>β has a similar function with mouse <italic>lnc-C/EBP</italic>β. Since MDSC subsets exert different suppressive function, <italic>lnc-C/EBP</italic>β may be acted as a potential therapeutic target for inflammatory and tumor-associated diseases.</p>