PMID- 19750015
OWN - NLM
STAT- MEDLINE
DCOM- 20100201
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 9
DP  - 2009 Sep 14
TI  - Interaction of polysialic acid with CCL21 regulates the migratory capacity of 
      human dendritic cells.
PG  - e6987
LID - 10.1371/journal.pone.0006987 [doi]
LID - e6987
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs). 
      Immature DCs (iDCs) are situated in the periphery where they capture pathogen. 
      Subsequently, they migrate as mature DCs (mDCs) to draining lymph nodes to 
      activate T cells. CCR7 and CCL21 contribute to the migratory capacity of the DC, 
      but it is not completely understood what molecular requirements are involved. 
      Here we demonstrate that monocyte-derived DCs dramatically change ST8Sia IV 
      expression during maturation, leading to the generation of polysialic acid 
      (polySia). PolySia expression is highly upregulated after 2 days Toll-like 
      receptor-4 (TLR4) triggering. Surprisingly, only immunogenic and not tolerogenic 
      mDCs upregulated polySia expression. Furthermore, we show that polySia expression 
      on DCs is required for CCL21-directed migration, whereby polySia directly 
      captures CCL21. Corresponding to polySia, the expression level of CCR7 is maximal 
      two days after TLR4 triggering. In contrast, although TLR agonists other than LPS 
      induce upregulation of CCR7, they achieve only a moderate polySia expression. In 
      situ we could detect polySia-expressing APCs in the T cell zone of the lymph node 
      and in the deep dermis. Together our results indicate that prolonged TLR4 
      engagement is required for the generation of polySia-expressing DCs that 
      facilitate CCL21 capture and subsequent CCL21-directed migration.
FAU - Bax, Marieke
AU  - Bax M
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Amsterdam, The Netherlands.
FAU - van Vliet, Sandra J
AU  - van Vliet SJ
FAU - Litjens, Manja
AU  - Litjens M
FAU - Garcia-Vallejo, Juan J
AU  - Garcia-Vallejo JJ
FAU - van Kooyk, Yvette
AU  - van Kooyk Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090914
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CCL21 protein, human)
RN  - 0 (CCR7 protein, human)
RN  - 0 (Chemokine CCL21)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Sialic Acids)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (polysialic acid)
RN  - EC 3.2.1.18 (Neuraminidase)
SB  - IM
MH  - Antigen-Presenting Cells/cytology
MH  - Cell Movement
MH  - Chemokine CCL21/metabolism/*physiology
MH  - Chemotaxis
MH  - Dendritic Cells/*cytology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Lymph Nodes/metabolism/pathology
MH  - Monocytes/cytology
MH  - Neuraminidase/metabolism
MH  - Protein Binding
MH  - Receptors, CCR7/metabolism
MH  - Sialic Acids/*metabolism
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC2737307
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/09/15 06:00
MHDA- 2010/02/02 06:00
PMCR- 2009/09/14
CRDT- 2009/09/15 06:00
PHST- 2009/05/07 00:00 [received]
PHST- 2009/08/13 00:00 [accepted]
PHST- 2009/09/15 06:00 [entrez]
PHST- 2009/09/15 06:00 [pubmed]
PHST- 2010/02/02 06:00 [medline]
PHST- 2009/09/14 00:00 [pmc-release]
AID - 09-PONE-RA-10197R1 [pii]
AID - 10.1371/journal.pone.0006987 [doi]
PST - epublish
SO  - PLoS One. 2009 Sep 14;4(9):e6987. doi: 10.1371/journal.pone.0006987.