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

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 and Teunis B. H. Geijtenbeek ()
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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

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6074

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