Lnc-C/EBPβ 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 CD11b Ly6C Ly6G monocytic MDSC (Mo-MDSC) and CD11b Ly6C Ly6G polymorphonuclear MDSC (PMN-MDSC) with different immunosuppressive function. However, it is poorly unde...

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Published inFrontiers in immunology Vol. 10; p. 1661
Main Authors Gao, Yunhuan, Shang, Wencong, Zhang, Dan, Zhang, Shiwu, Zhang, Xipeng, Zhang, Yuan, Yang, Rongcun
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 17.07.2019
Subjects
H3K4me3
IL4il
Immunology
lncRNA
MDSC
WDR5
WDR5
MDSC
lncRNA
IL4il
H3K4me3
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Abstract Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b Ly6C Ly6G monocytic MDSC (Mo-MDSC) and CD11b Ly6C Ly6G 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.
AbstractList 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.
Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b + Ly6C hi Ly6G − monocytic MDSC (Mo-MDSC) and CD11b + Ly6C low/neg Ly6G + 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 β may promote PMN-MDSC but impede differentiation of Mo-MDSCs in vitro and in vivo . We demonstrated that lnc-C/EBP β mediated differentiation of MDSCs was through downregulating multiple transcripts such as IL4il. Lnc-C/EBP 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 lnc-C/EBP β has a similar function with mouse lnc-C/EBP β. Since MDSC subsets exert different suppressive function, lnc-C/EBP β may be acted as a potential therapeutic target for inflammatory and tumor-associated diseases.
Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b Ly6C Ly6G monocytic MDSC (Mo-MDSC) and CD11b Ly6C Ly6G 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.
Author Zhang, Shiwu
Zhang, Xipeng
Zhang, Yuan
Zhang, Dan
Gao, Yunhuan
Shang, Wencong
Yang, Rongcun
AuthorAffiliation 3 Department of Immunology, Nankai University School of Medicine, Nankai University , Tianjin , China
5 Department of Colorectal Surgery, Tianjin Union Medical Center , Tianjin , China
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
4 Department of Pathology, Tianjin Union Medical Center , Tianjin , China
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Keywords WDR5
MDSC
lncRNA
IL4il
H3K4me3
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This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology
Reviewed by: Tomokatsu Ikawa, Tokyo University of Science, Japan; Jun Lu, Yale University, United States
Edited by: Shohei Hori, The University of Tokyo, Japan
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Snippet Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b Ly6C Ly6G...
Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b + Ly6C hi Ly6G −...
Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11b+Ly6ChiLy6G−...
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SubjectTerms H3K4me3
IL4il
Immunology
lncRNA
MDSC
WDR5
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Title Lnc-C/EBPβ Modulates Differentiation of MDSCs Through Downregulating IL4i1 With C/EBPβ LIP and WDR5
URI https://www.ncbi.nlm.nih.gov/pubmed/31379854
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