PMID- 25278262
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20171116
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 5
DP  - 2014 Oct 3
TI  - Fucose-based PAMPs prime dendritic cells for follicular T helper cell 
      polarization via DC-SIGN-dependent IL-27 production.
PG  - 5074
LID - 10.1038/ncomms6074 [doi]
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 IKKepsilon, 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.
FAU - Gringhuis, Sonja I
AU  - Gringhuis SI
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
FAU - Kaptein, Tanja M
AU  - Kaptein TM
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
FAU - Wevers, Brigitte A
AU  - Wevers BA
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
FAU - van der Vlist, Michiel
AU  - van der Vlist M
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
FAU - Klaver, Elsenoor J
AU  - Klaver EJ
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
FAU - van Die, Irma
AU  - van Die I
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
FAU - Vriend, Lianne E M
AU  - Vriend LE
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
FAU - de Jong, Marein A W P
AU  - de Jong MA
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
FAU - Geijtenbeek, Teunis B H
AU  - Geijtenbeek TB
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141003
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (BCL6 protein, human)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IRF7 protein, human)
RN  - 0 (IRF9 protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interferon Regulatory Factor-7)
RN  - 0 (Interferon-Stimulated Gene Factor 3, gamma Subunit)
RN  - 0 (Interleukin-27)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 0 (Receptors, Cell Surface)
RN  - 28RYY2IV3F (Fucose)
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Amino Acid Motifs
MH  - B-Lymphocytes/cytology
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Differentiation
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Dendritic Cells/*cytology
MH  - Dimerization
MH  - Flow Cytometry
MH  - Fucose/*chemistry
MH  - Humans
MH  - Immunoglobulin G/chemistry
MH  - Interferon Regulatory Factor-7/metabolism
MH  - Interferon-Stimulated Gene Factor 3, gamma Subunit/*metabolism
MH  - Interleukin-27/*metabolism
MH  - Lectins, C-Type/*metabolism
MH  - Leukocytes, Mononuclear/cytology
MH  - Lymphocyte Activation/immunology
MH  - Mannose/chemistry
MH  - Proto-Oncogene Proteins c-bcl-6
MH  - RNA Interference
MH  - Receptors, Cell Surface/*metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Helper-Inducer/*cytology
EDAT- 2014/10/04 06:00
MHDA- 2015/12/17 06:00
CRDT- 2014/10/04 06:00
PHST- 2014/05/26 00:00 [received]
PHST- 2014/08/25 00:00 [accepted]
PHST- 2014/10/04 06:00 [entrez]
PHST- 2014/10/04 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - ncomms6074 [pii]
AID - 10.1038/ncomms6074 [doi]
PST - epublish
SO  - Nat Commun. 2014 Oct 3;5:5074. doi: 10.1038/ncomms6074.