1. Academic Validation
  2. Tumor Environment Promotes Lnc57Rik-Mediated Suppressive Function of Myeloid-Derived Suppressor Cells

Tumor Environment Promotes Lnc57Rik-Mediated Suppressive Function of Myeloid-Derived Suppressor Cells

  • J Immunol. 2022 Oct 1;209(7):1401-1413. doi: 10.4049/jimmunol.2200195.
Ya Wang 1 Yunhuan Gao 1 Chunze Zhang 2 Jianmei Yue 1 Rong Wang 1 Hang Liu 1 Xiaorong Yang 1 Yuan Zhang 1 Rongcun Yang 3 4 5
Affiliations

Affiliations

  • 1 Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China.
  • 2 Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
  • 3 Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China; ryang@nankai.edu.cn.
  • 4 Translational Medicine Institute, Tianjin Union Medical Center of Nankai University, Tianjin, China; and.
  • 5 State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
Abstract

Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes with potent immunosuppressive activity that regulate immune responses in the tumor microenvironment. We identified a novel long noncoding RNA (lncRNA), named as lnc57Rik, in the MDSCs that controls their immunosuppressive functions. Lnc57Rik was induced in in vitro and in vivo inflammatory settings and upregulated the genes related to MDSC-mediated immunosuppression, including Arg-1, NOS2, NOX2, and COX2 Furthermore, Lnc57Rik can not only bind with the C/EBPβ isoform liver-enriched activator protein to activate C/EBPβ but also with the methyltransferase WD repeat-containing protein 5 that enables the enrichment of histone H3 trimethylated lysine 4 marks on the promoter regions of Arg-1, NOS2, NOX2, and COX2, eventually resulting in their transcriptional activation. Furthermore, the conserved human lnc57Rik has a similar function as murine lnc57Rik Taken together, upregulation of lnc57Rik in the tumor microenvironment promotes the immunosuppressive function of MDSCs.

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