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

Journal: Nature communications 2015;5():5074

PMID: 25278262

Free Full Text on Nature Publishing Group View on PubMed

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-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.

Address: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.; Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.

DOI: 10.1038/ncomms6074

Link outs

Free resources

Full Text Sources:

https://doi.org/10.1038/ncomms6074

Other Literature Sources:

MeSH Terms: Amino Acid Motifs, B-Lymphocytes, Cell Adhesion Molecules, Cell Differentiation, Cell Nucleus, DNA-Binding Proteins, Dendritic Cells, Dimerization, Flow Cytometry, Fucose, Humans, Immunoglobulin G, Interferon Regulatory Factor-7, Interferon-Stimulated Gene Factor 3, gamma Subunit, Interleukin-27, Lectins, C-Type, Leukocytes, Mononuclear, Lymphocyte Activation, Mannose, Proto-Oncogene Proteins c-bcl-6, RNA Interference, Receptors, Cell Surface, Signal Transduction, T-Lymphocytes, Helper-Inducer