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

Yunhuan Gao; Wencong Shang; Dan Zhang; Shiwu Zhang; Xipeng Zhang; Yuan Zhang; Rongcun Yang

doi:10.3389/fimmu.2019.01661

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

Front Immunol. 2019 Jul 17:10:1661. doi: 10.3389/fimmu.2019.01661. eCollection 2019.

Authors

Yunhuan Gao^{1

2

3}, Wencong Shang^{1

2

3}, Dan Zhang⁴, Shiwu Zhang⁴, Xipeng Zhang⁵, Yuan Zhang^{1

2

3}, Rongcun Yang^{1

2

3}

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
² Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.
³ Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China.
⁴ Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
⁵ Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.

Abstract

Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b⁺Ly6C^hiLy6G^- monocytic MDSC (Mo-MDSC) and CD11b⁺Ly6C^low/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/EBPβ may promote PMN-MDSC but impede differentiation of Mo-MDSCs in vitro and in vivo. We demonstrated that lnc-C/EBPβ mediated differentiation of MDSCs was through downregulating multiple transcripts such as IL4il. Lnc-C/EBPβ 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 lnc-C/EBPβ has a similar function with mouse lnc-C/EBPβ. Since MDSC subsets exert different suppressive function, lnc-C/EBPβ may be acted as a potential therapeutic target for inflammatory and tumor-associated diseases.

Keywords: H3K4me3; IL4il; MDSC; WDR5; lncRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CCAAT-Enhancer-Binding Protein-beta / metabolism*
Cell Differentiation / physiology*
Cell Line
Down-Regulation / physiology*
Histones / metabolism
Humans
Inflammation / immunology
Intracellular Signaling Peptides and Proteins / metabolism*
L-Amino Acid Oxidase / metabolism*
Mice
Mice, Inbred C57BL
Monocytes / metabolism
Myeloid Cells / metabolism
Myeloid-Derived Suppressor Cells / metabolism*
Neoplasms / metabolism
Promoter Regions, Genetic / physiology

Substances

CCAAT-Enhancer-Binding Protein-beta
CEBPB protein, human
Histones
Intracellular Signaling Peptides and Proteins
WDR5 protein, human
histone H3 trimethyl Lys4
IL4I1 protein, human
L-Amino Acid Oxidase