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

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 (T FH ) 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 T FH cells, IL-21 secretion by T FH 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 T FH polarization, which might be harnessed for vaccination design. Dendritic cells (DCs) initiate distinct arms of immunity in response to different classes of pathogens. Here Gringhuis et al . show that DCs produce IL-27 upon sensing fucose-containing pathogen ligands via DC-SIGN, promoting follicular T helper cell differentiation and antibody production.