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

Frontiers in Immunology
Yunhuan GaoRongcun Yang

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/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.

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Citations

Sep 29, 2020·Frontiers in Immunology·Elliot D Kramer, Scott I Abrams
May 19, 2020·The Journal of Clinical Investigation·Anca DorhoiNelita du Plessis
Nov 3, 2020·Frontiers in Immunology·Elham SafarzadehBehzad Baradaran
Nov 6, 2020·Journal of Experimental & Clinical Cancer Research : CR·Yalu ZhangQuan Liao
Feb 17, 2021·Cellular Immunology·Maria Dulfary Sanchez-PinoAugusto C Ochoa
May 21, 2021·Transplant Immunology·Yao TengQiuling Wu

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Datasets Mentioned

BETA
GSE104571
GM-CSF
GSE104558

Methods Mentioned

BETA
PCR
Fluorescence
Immunoprecipitation-PCR
immunoprecipitation
pull-down
in vitro transcription
flow cytometry
transfect
Confocal microscopy
RIP

Software Mentioned

Genome
browser
Score Designer
BLOCK
IP
R
GraphPad Prism
limma
[UNK] RNAi Designer
MASS

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