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

Nicholas J. Hess, Christopher Felicelli, Jennifer Grage, Richard I. Tapping

Research output: Contribution to journalArticle

Abstract

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 aTLR10 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-g 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.

Original languageEnglish (US)
Pages (from-to)1245-1252
Number of pages8
JournalJournal of Leukocyte Biology
Volume101
Issue number5
DOIs
StatePublished - May 2017

Keywords

  • Cytokines
  • Regulation
  • TLR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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