The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation

Science. 2014 Apr 18;344(6181):310-3. doi: 10.1126/science.1251456.


Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes; however, few have been identified that regulate immune cell differentiation and function. Here, we identified lnc-DC, which was exclusively expressed in human conventional dendritic cells (DCs). Knockdown of lnc-DC impaired DC differentiation from human monocytes in vitro and from mouse bone marrow cells in vivo and reduced capacity of DCs to stimulate T cell activation. lnc-DC mediated these effects by activating the transcription factor STAT3 (signal transducer and activator of transcription 3). lnc-DC bound directly to STAT3 in the cytoplasm, which promoted STAT3 phosphorylation on tyrosine-705 by preventing STAT3 binding to and dephosphorylation by SHP1. Our work identifies a lncRNA that regulates DC differentiation and also broadens the known mechanisms of lncRNA action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • Chromatin / metabolism
  • Cytoplasm / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Epigenesis, Genetic
  • Gene Expression Regulation
  • Histones / metabolism
  • Humans
  • Lymphocyte Activation
  • Mice
  • Monocytes / cytology
  • Nucleic Acid Conformation
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • RNA, Long Noncoding / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • T-Lymphocytes / immunology


  • Chromatin
  • Histones
  • RNA, Long Noncoding
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6

Associated data

  • GEO/GSE43036
  • GEO/GSE54143
  • GEO/GSE54401