Frontiers in Immunology (Jul 2019)

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

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

DOI
https://doi.org/10.3389/fimmu.2019.01661
Journal volume & issue
Vol. 10

Abstract

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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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