TLR10 suppresses the activation and differentiation of monocytes with effects on DC-mediated adaptive immune responses

J Leukoc Biol. 2017 May;101(5):1245-1252. doi: 10.1189/jlb.3A1116-492R. Epub 2017 Feb 24.


TLRs are important pattern-recognition receptors involved in the activation of innate immune responses against foreign pathogens. TLR10 is the only TLR family member without a known ligand, signaling pathway, or clear cellular function. Previous work has shown that TLR10 suppresses proinflammatory cytokine production in response to TLR agonists in a mixed human mononuclear cell population. We report that TLR10 is preferentially expressed on monocytes and suppresses proinflammatory cytokine production resulting from either TLR or CD40 stimulation. TLR10 engagement affects both the MAPK and Akt signaling pathways, leading to changes in the transcriptome of isolated human monocytes. Differentiation of monocytes into dendritic cells in the presence of an αTLR10 mAb reduced the expression of maturation markers and the induction of proinflammatory cytokines, again in response to either TLR or CD40 stimulation. Finally, in coculture experiments, TLR10 differentiated dendritic cells exhibited a decreased capacity to activate T cells as measured by IL-2 and IFN-γ production. These data demonstrate that TLR10 is a novel regulator of innate immune responses and of the differentiation of primary human monocytes into effective dendritic cells.

Keywords: TLR; cytokines; regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Antibodies, Monoclonal / pharmacology
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology
  • Cell Differentiation
  • Coculture Techniques
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / immunology
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Toll-Like Receptor 10 / agonists
  • Toll-Like Receptor 10 / genetics
  • Toll-Like Receptor 10 / immunology*
  • Transcriptome / genetics
  • Transcriptome / immunology*


  • Antibodies, Monoclonal
  • CD40 Antigens
  • IFNG protein, human
  • Interleukin-2
  • TLR10 protein, human
  • Toll-Like Receptor 10
  • Interferon-gamma
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases