Induction of an anti-inflammatory cytokine, IL-10, in dendritic cells after toll-like receptor signaling

J Interferon Cytokine Res. 2006 Dec;26(12):893-900. doi: 10.1089/jir.2006.26.893.


Interleukin-10 (IL-10) is an anti-inflammatory cytokine that modulates innate and adaptive immunity. IL-10 transcripts and the protein were induced in murine bone marrow-derived dendritic cells (BMDCs) after toll-like receptor (TLR) stimulation. IL-10 induction was TLR ligand selective, in that CpG DNA, imidazoquinolin, peptidoglycan, and zymosan but not lipopolysaccharide (LPS) and poly I:C led to IL-10 production. IL-10 induction was, however, completely absent in MyD88(/) DCs that lacked a TLR adaptor showing that IL-10 induction depends on TLR signaling. Kinetic analysis of IL-10 induction by CpG and imidazoquinolin revealed a prolonged lag phase prior to a measurable rise in transcript levels, which peaked at 12-24 h after stimulation. Stat3, implicated in IL-10 gene transcription, was also induced after TLR stimulation with the kinetics similar to those of IL-10 induction. Further, Stat3 was phosphorylated and bound to the IL-10 promoter in TLR-stimulated DCs. Supporting a link with IL-10 induction, STAT3 induction was absent in MyD88(/) DCs. These data suggest a two-step model where the initial TLR signaling induced proinflammatory cytokines, which then activated Stat3, leading to the induction of IL-10. TLR-stimulated IL-10 production may regulate DC maturation steps, thereby influencing the ensuing immune responses.

MeSH terms

  • Animals
  • Autocrine Communication
  • Dendritic Cells / immunology*
  • Gene Expression Regulation*
  • Imidazoles / pharmacology
  • Inflammation / immunology
  • Interleukin-10 / analysis
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Ligands
  • Mice
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / physiology
  • Oligodeoxyribonucleotides / pharmacology
  • Paracrine Communication
  • Peptidoglycan / pharmacology
  • Poly I-C / pharmacology
  • Promoter Regions, Genetic
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / physiology*
  • Transcription, Genetic
  • Transcriptional Activation
  • Zymosan / pharmacology


  • CPG-oligonucleotide
  • Imidazoles
  • Ligands
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Oligodeoxyribonucleotides
  • Peptidoglycan
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Toll-Like Receptors
  • Interleukin-10
  • Zymosan
  • Poly I-C