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

doi:10.1038/ncomms6074

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

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	5074
Journal	Nature Communications [E]
Volume	5
DOIs	https://doi.org/10.1038/ncomms6074
Publication status	Published - 2014

Keywords

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
RNA Interference
Receptors, Cell Surface
Signal Transduction
T-Lymphocytes, Helper-Inducer

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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.",

keywords = "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, RNA Interference, Receptors, Cell Surface, Signal Transduction, T-Lymphocytes, Helper-Inducer",

author = "Gringhuis, {Sonja I} and Kaptein, {Tanja M} and Wevers, {Brigitte A} and {van der Vlist}, Michiel and Klaver, {Elsenoor J} and {van Die}, Irma and Vriend, {Lianne E M} and {de Jong}, {Marein A W P} and Geijtenbeek, {Teunis B H}",

year = "2014",

doi = "10.1038/ncomms6074",

language = "English",

volume = "5",

pages = "5074",

journal = "Nature Communications [E]",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production

AU - Gringhuis, Sonja I

AU - Kaptein, Tanja M

AU - Wevers, Brigitte A

AU - van der Vlist, Michiel

AU - Klaver, Elsenoor J

AU - van Die, Irma

AU - Vriend, Lianne E M

AU - de Jong, Marein A W P

AU - Geijtenbeek, Teunis B H

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Amino Acid Motifs

KW - B-Lymphocytes

KW - Cell Adhesion Molecules

KW - Cell Differentiation

KW - Cell Nucleus

KW - DNA-Binding Proteins

KW - Dendritic Cells

KW - Dimerization

KW - Flow Cytometry

KW - Fucose

KW - Humans

KW - Immunoglobulin G

KW - Interferon Regulatory Factor-7

KW - Interferon-Stimulated Gene Factor 3, gamma Subunit

KW - Interleukin-27

KW - Lectins, C-Type

KW - Leukocytes, Mononuclear

KW - Lymphocyte Activation

KW - Mannose

KW - RNA Interference

KW - Receptors, Cell Surface

KW - Signal Transduction

KW - T-Lymphocytes, Helper-Inducer

U2 - 10.1038/ncomms6074

DO - 10.1038/ncomms6074

M3 - Article

C2 - 25278262

SN - 2041-1723

VL - 5

SP - 5074

JO - Nature Communications [E]

JF - Nature Communications [E]

ER -

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

Abstract

Keywords

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