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Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production

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Listed:
  • Sonja I. Gringhuis

    (Academic Medical Center, University of Amsterdam)

  • Tanja M. Kaptein

    (Academic Medical Center, University of Amsterdam)

  • Brigitte A. Wevers

    (Academic Medical Center, University of Amsterdam)

  • Michiel van der Vlist

    (Academic Medical Center, University of Amsterdam)

  • Elsenoor J. Klaver

    (VU University Medical Center)

  • Irma van Die

    (VU University Medical Center)

  • Lianne E. M. Vriend

    (Academic Medical Center, University of Amsterdam)

  • Marein A. W. P. de Jong

    (Academic Medical Center, University of Amsterdam)

  • Teunis B. H. Geijtenbeek

    (Academic Medical Center, University of Amsterdam)

Abstract

Dendritic cells (DCs) orchestrate antibody-mediated responses to combat extracellular pathogens including parasites by initiating T helper cell differentiation. Here we demonstrate that carbohydrate-specific signalling by DC-SIGN drives follicular T helper cell (TFH) differentiation via IL-27 expression. Fucose, but not mannose, engagement of DC-SIGN results in activation of IKKε, which collaborates with type I IFNR signalling to induce formation and activation of transcription factor ISGF3. Notably, ISGF3 induces expression of IL-27 subunit p28, and subsequent IL-27 secreted by DC-SIGN-primed DCs is pivotal for the induction of Bcl-6+CXCR5+PD-1hiFoxp1lo TFH cells, IL-21 secretion by TFH cells and T-cell-dependent IgG production by B cells. Thus, we have identified an essential role for DC-SIGN-induced ISGF3 by fucose-based PAMPs in driving IL-27 and subsequent TFH polarization, which might be harnessed for vaccination design.

Suggested Citation

  • Sonja I. Gringhuis & Tanja M. Kaptein & Brigitte A. Wevers & Michiel van der Vlist & Elsenoor J. Klaver & Irma van Die & Lianne E. M. Vriend & Marein A. W. P. de Jong & Teunis B. H. Geijtenbeek, 2014. "Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6074
    DOI: 10.1038/ncomms6074
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    1. Alexiane Decout & Ioannis Krasias & Lauren Roberts & Belen Gimeno Molina & Chloé Charenton & Daniel Brown Romero & Qiong Y. Tee & Julian R. Marchesi & Sherrianne Ng & Lynne Sykes & Phillip R. Bennett , 2024. "Lactobacillus crispatus S-layer proteins modulate innate immune response and inflammation in the lower female reproductive tract," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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