PMID- 20483748
OWN - NLM
STAT- MEDLINE
DCOM- 20100618
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 184
IP  - 12
DP  - 2010 Jun 15
TI  - Alpha4beta1 integrin mediates the recruitment of immature dendritic cells across 
      the blood-brain barrier during experimental autoimmune encephalomyelitis.
PG  - 7196-206
LID - 10.4049/jimmunol.0901404 [doi]
AB  - Dendritic cells (DCs) within the CNS are recognized to play an important role in 
      the effector phase and propagation of the immune response in experimental 
      autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. 
      However, the mechanisms regulating DC trafficking into the CNS still need to be 
      characterized. In this study, we show by performing intravital fluorescence 
      videomicroscopy of the inflamed spinal cord white-matter microvasculature in SJL 
      mice with EAE that immature, and to a lesser extent, LPS-matured, bone 
      marrow-derived DCs efficiently interact with the CNS endothelium by rolling, 
      capturing, and firm adhesion. Immature but not LPS-matured DCs efficiently 
      migrated across the wall of inflamed parenchymal microvessels into the CNS. 
      Blocking alpha4 integrins interfered with the adhesion but not the rolling or 
      capturing of immature and LPS-matured DCs to the CNS microvascular endothelium, 
      inhibiting their migration across the vascular wall. Functional absence of beta1 
      integrins but not of beta7 integrins or alpha4beta7 integrin similarly reduced 
      the adhesion of immature DCs to the CNS microvascular endothelium, demonstrating 
      that alpha4beta1 but not alpha4beta7 integrin mediates this step of immature DCs 
      interaction with the inflamed blood-brain barrier during EAE. Our study shows 
      that during EAE, especially immature DCs migrate into the CNS, where they may be 
      crucial for the perpetuation of the CNS-targeted autoimmune response. Thus 
      therapeutic targeting of alpha4 integrins affects DC trafficking into the CNS and 
      may therefore lead to the resolution of the CNS autoimmune inflammation by 
      reducing the number of CNS professional APCs.
FAU - Jain, Pooja
AU  - Jain P
AD  - Department of Microbiology and Immunology and Drexel Institute for Biotechnology 
      and Virology Research, Drexel University College of Medicine, Doylestown, PA 
      18902, USA. pjain@drexelmed.edu
FAU - Coisne, Caroline
AU  - Coisne C
FAU - Enzmann, Gaby
AU  - Enzmann G
FAU - Rottapel, Robert
AU  - Rottapel R
FAU - Engelhardt, Britta
AU  - Engelhardt B
LA  - eng
GR  - R01 AI077414/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100517
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Integrin alpha4beta1)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/immunology/*metabolism
MH  - Cell Separation
MH  - Chemotaxis, Leukocyte/*immunology
MH  - Dendritic Cells/immunology/*metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/immunology/*metabolism/pathology
MH  - Female
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Integrin alpha4beta1/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Fluorescence
MH  - Spinal Cord/immunology/pathology
PMC - PMC3999618
MID - NIHMS570485
COIS- Disclosures The authors have no financial conflicts of interest.
EDAT- 2010/05/21 06:00
MHDA- 2010/06/19 06:00
PMCR- 2014/04/25
CRDT- 2010/05/21 06:00
PHST- 2010/05/21 06:00 [entrez]
PHST- 2010/05/21 06:00 [pubmed]
PHST- 2010/06/19 06:00 [medline]
PHST- 2014/04/25 00:00 [pmc-release]
AID - jimmunol.0901404 [pii]
AID - 10.4049/jimmunol.0901404 [doi]
PST - ppublish
SO  - J Immunol. 2010 Jun 15;184(12):7196-206. doi: 10.4049/jimmunol.0901404. Epub 2010 
      May 17.