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, Teunis B. H. Geijtenbeek

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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-1(hi)Foxp1(lo) 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
Original languageEnglish
Article number5074
Pages (from-to)5074
JournalNature communications
Publication statusPublished - 2014

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