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Antibody Profiling by Luciferase Immunoprecipitation Systems LIPS
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Lnc-C/EBPβ Modulates Differentiation of MDSCs Through Downregulating IL4i1 With C/EBPβ LIP and WDR5

Yunhuan Gao1,2,3, Wencong Shang1,2,3, Dan Zhang4

  • 1State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.

Frontiers in Immunology
|August 6, 2019
PubMed

Insights

A novel long non-coding RNA, lnc-C/EBPβ, regulates myeloid-derived suppressor cell (MDSC) differentiation. It promotes polymorphonuclear MDSCs (PMN-MDSCs) while hindering monocytic MDSCs (Mo-MDSCs), offering a potential therapeutic target.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Myeloid-derived suppressor cells (MDSCs) are crucial in tumor and inflammatory diseases.
  • MDSCs comprise monocytic (Mo-MDSC) and polymorphonuclear (PMN-MDSC) subsets with distinct immunosuppressive functions.
  • Mechanisms controlling MDSC subset differentiation remain largely unknown.

Purpose of the Study:

  • To investigate the role of lnc-C/EBPβ in regulating Mo-MDSC and PMN-MDSC differentiation.
  • To elucidate the molecular mechanisms by which lnc-C/EBPβ controls MDSC subset development.

Main Methods:

  • In vitro and in vivo differentiation assays.
  • RNA sequencing and transcriptomic analysis to identify downstream targets.
  • Chromatin immunoprecipitation and biochemical assays to determine molecular interactions.

Main Results:

  • lnc-C/EBPβ promotes PMN-MDSC differentiation and impedes Mo-MDSC differentiation.
  • lnc-C/EBPβ downregulates IL4i1 expression, a key transcript in MDSC differentiation.
  • lnc-C/EBPβ interacts with C/EBPβ and WDR5, inhibiting C/EBPβ activation and H3K4me3 enrichment at the IL4i1 promoter.

Conclusions:

  • lnc-C/EBPβ is a critical regulator of MDSC subset differentiation.
  • The findings reveal a novel mechanism controlling MDSC development.
  • lnc-C/EBPβ represents a potential therapeutic target for inflammatory and tumor-associated diseases.
Keywords:
H3K4me3IL4ilMDSCWDR5lncRNA

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