PMID- 24493818
OWN - NLM
STAT- MEDLINE
DCOM- 20140418
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 192
IP  - 5
DP  - 2014 Mar 1
TI  - Lymphatic specific disruption in the fine structure of heparan sulfate inhibits 
      dendritic cell traffic and functional T cell responses in the lymph node.
PG  - 2133-42
LID - 10.4049/jimmunol.1301286 [doi]
AB  - Dendritic cells (DCs) are potent APCs essential for initiating adaptive immunity. 
      Following pathogen exposure, trafficking of DCs to lymph nodes (LNs) through 
      afferent lymphatic vessels constitutes a crucial step in the execution of their 
      functions. The mechanisms regulating this process are poorly understood, although 
      the involvement of certain chemokines in this process has recently been reported. 
      In this study, we demonstrate that genetically altering the fine structure 
      (N-sulfation) of heparan sulfate (HS) specifically in mouse lymphatic endothelium 
      significantly reduces DC trafficking to regional LNs in vivo. Moreover, this 
      alteration had the unique functional consequence of reducing CD8(+) T cell 
      proliferative responses in draining LNs in an ovalbumin immunization model. 
      Mechanistic studies suggested that lymphatic endothelial HS regulates multiple 
      steps during DC trafficking, including optimal presentation of chemokines on the 
      surface of DCs, thus acting as a co-receptor that may function "in trans" to 
      mediate chemokine receptor binding. This study not only identifies novel 
      glycan-mediated mechanisms that regulate lymphatic DC trafficking, but it also 
      validates the fine structure of lymphatic vascular-specific HS as a novel 
      molecular target for strategies aiming to modulate DC behavior and/or alter 
      pathologic T cell responses in lymph nodes.
FAU - Yin, Xin
AU  - Yin X
AD  - Marine Drug Research Institute, Huaihai Institute of Technology, Lianyungang 
      222005, China;
FAU - Johns, Scott C
AU  - Johns SC
FAU - Kim, Daniel
AU  - Kim D
FAU - Mikulski, Zbigniew
AU  - Mikulski Z
FAU - Salanga, Catherina L
AU  - Salanga CL
FAU - Handel, Tracy M
AU  - Handel TM
FAU - Macal, Monica
AU  - Macal M
FAU - Zuniga, Elina I
AU  - Zuniga EI
FAU - Fuster, Mark M
AU  - Fuster MM
LA  - eng
GR  - R01-AI37113/AI/NIAID NIH HHS/United States
GR  - T32HL098062/HL/NHLBI NIH HHS/United States
GR  - T32 HL098062/HL/NHLBI NIH HHS/United States
GR  - P01 HL57345-14/HL/NHLBI NIH HHS/United States
GR  - R21-AI102247/AI/NIAID NIH HHS/United States
GR  - R01 HL107652/HL/NHLBI NIH HHS/United States
GR  - R01 AI081923/AI/NIAID NIH HHS/United States
GR  - R01-HL107652-01A1/HL/NHLBI NIH HHS/United States
GR  - R21 AI102247/AI/NIAID NIH HHS/United States
GR  - R01-081923/PHS HHS/United States
GR  - I01 BX000987/BX/BLRD VA/United States
GR  - P01 HL057345/HL/NHLBI NIH HHS/United States
GR  - R01 AI037113/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140203
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokines)
RN  - 9050-30-0 (Heparitin Sulfate)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology
MH  - Cell Movement/genetics/*immunology
MH  - Chemokines/genetics/immunology
MH  - Dendritic Cells/cytology/*immunology
MH  - Endothelium, Lymphatic/cytology/*immunology
MH  - Heparitin Sulfate/genetics/*immunology
MH  - Humans
MH  - Lymph Nodes/cytology/*immunology
MH  - Mice
MH  - Mice, Transgenic
PMC - PMC3960083
MID - NIHMS552473
EDAT- 2014/02/05 06:00
MHDA- 2014/04/20 06:00
PMCR- 2015/03/01
CRDT- 2014/02/05 06:00
PHST- 2014/02/05 06:00 [entrez]
PHST- 2014/02/05 06:00 [pubmed]
PHST- 2014/04/20 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - jimmunol.1301286 [pii]
AID - 10.4049/jimmunol.1301286 [doi]
PST - ppublish
SO  - J Immunol. 2014 Mar 1;192(5):2133-42. doi: 10.4049/jimmunol.1301286. Epub 2014 
      Feb 3.