title: Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production.
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.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Gringhuis
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Kaptein
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
authors.forename: Brigitte A
authors.initials: BA
authors.lastname: Wevers
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Vlist
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: Elsenoor J
authors.initials: EJ
authors.lastname: Klaver
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
authors.forename: Lianne E M
authors.initials: LE
authors.lastname: Vriend
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
authors.forename: Marein A W P
authors.initials: MA
authors.lastname: de Jong
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D020816:Amino Acid Motifs; D001402:B-Lymphocytes / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D019281:Dimerization; D005434:Flow Cytometry; D005643:Fucose / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000378:metabolism*; D064094:Interleukin-27 / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D008358:Mannose / Q000737:chemistry; D051560:Proto-Oncogene Proteins c-bcl-6; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D005643:Fucose; D007074:Immunoglobulin G; D050839:Interferon Regulatory Factor-7; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D064094:Interleukin-27; D037181:Lectins, C-Type; D008358:Mannose; D051560:Proto-Oncogene Proteins c-bcl-6; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C084103:BCL6 protein, human; C494234:IRF7 protein, human; C494227:IRF9 protein, human