Human CD4
Adhesion molecule
Blood-cerebrospinal fluid barrier
Blood–brain barrier
Multiple sclerosis
T-cell migration
Journal
Fluids and barriers of the CNS
ISSN: 2045-8118
Titre abrégé: Fluids Barriers CNS
Pays: England
ID NLM: 101553157
Informations de publication
Date de publication:
03 Feb 2020
03 Feb 2020
Historique:
received:
13
11
2019
accepted:
19
12
2019
entrez:
4
2
2020
pubmed:
6
2
2020
medline:
20
11
2020
Statut:
epublish
Résumé
The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood-brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP). Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4 Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4 While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration. Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.
Sections du résumé
BACKGROUND
BACKGROUND
The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood-brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP).
OBJECTIVE
OBJECTIVE
Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4
METHODS
METHODS
Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4
RESULTS
RESULTS
While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration.
CONCLUSIONS
CONCLUSIONS
Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.
Identifiants
pubmed: 32008573
doi: 10.1186/s12987-019-0165-2
pii: 10.1186/s12987-019-0165-2
pmc: PMC6996191
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL046849
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL064774
Pays : United States
Organisme : Swiss National Science Foundation
ID : CRSII3_154483
Pays : Switzerland
Références
Fluids Barriers CNS. 2013 Jan 10;10(1):1
pubmed: 23305147
Microbes Infect. 2013 Apr;15(4):291-301
pubmed: 23376167
Eur J Immunol. 2016 Sep;46(9):2187-203
pubmed: 27338806
Lancet Oncol. 2009 Aug;10(8):816-24
pubmed: 19647202
J Immunol. 2010 Oct 15;185(8):4846-55
pubmed: 20861356
J Vis Exp. 2016 May 06;(111):
pubmed: 27213495
Am J Pathol. 1996 Jun;148(6):1819-38
pubmed: 8669469
Brain. 2018 Jul 1;141(7):2066-2082
pubmed: 29873694
Cell. 2018 Nov 29;175(6):1679-1687.e7
pubmed: 30343897
Front Immunol. 2017 Apr 11;8:406
pubmed: 28443093
J Immunol. 2011 Dec 15;187(12):6176-9
pubmed: 22084440
Science. 2015 Jan 23;347(6220):400-6
pubmed: 25477212
J Exp Med. 1998 Mar 16;187(6):875-83
pubmed: 9500790
Ann Neurol. 2009 Sep;66(3):390-402
pubmed: 19810097
Brain. 2011 Sep;134(Pt 9):2687-702
pubmed: 21908874
Lancet. 2018 Apr 21;391(10130):1622-1636
pubmed: 29576504
Front Immunol. 2019 Apr 05;10:711
pubmed: 31024547
Brain. 2013 Nov;136(Pt 11):3427-40
pubmed: 24088808
PLoS One. 2016 Mar 04;11(3):e0150945
pubmed: 26942913
Eur J Immunol. 1998 Sep;28(9):2760-9
pubmed: 9754563
Sci Rep. 2019 Jan 18;9(1):203
pubmed: 30659216
PLoS One. 2012;7(1):e30069
pubmed: 22253884
Nat Med. 2008 Mar;14(3):337-42
pubmed: 18278054
Fluids Barriers CNS. 2012 Aug 07;9(1):15
pubmed: 22870943
Nat Immunol. 2009 May;10(5):514-23
pubmed: 19305396
J Neuropathol Exp Neurol. 2003 Apr;62(4):412-9
pubmed: 12722833
Nat Immunol. 2017 Feb;18(2):123-131
pubmed: 28092374
J Immunol. 2003 May 1;170(9):4497-505
pubmed: 12707326
Nat Immunol. 2002 Feb;3(2):143-50
pubmed: 11812991
J Exp Med. 2011 Nov 21;208(12):2465-76
pubmed: 22025301
Neuroscience. 2019 Apr 1;403:136-144
pubmed: 29273325
Lab Invest. 2005 Jun;85(6):734-46
pubmed: 15908914
J Exp Med. 2008 Oct 27;205(11):2633-42
pubmed: 18852291
Trends Immunol. 2012 Dec;33(12):579-89
pubmed: 22926201
Front Immunol. 2018 May 16;9:1066
pubmed: 29868025
Lab Invest. 2016 May;96(5):588-98
pubmed: 26901835
J Neurosci. 1999 Aug 1;19(15):6275-89
pubmed: 10414957
Sci Rep. 2019 Jul 11;9(1):10046
pubmed: 31296913
ASN Neuro. 2013;5(1):e00110
pubmed: 23452162
Cell Mol Immunol. 2019 Jul;16(7):652-665
pubmed: 30635649
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8389-94
pubmed: 12829791
Cell. 2018 Sep 20;175(1):85-100.e23
pubmed: 30173916
J Neuroimmunol. 2007 Mar;184(1-2):136-48
pubmed: 17291598
J Leukoc Biol. 2003 May;73(5):584-90
pubmed: 12714572
Virus Res. 2017 Mar 15;232:54-62
pubmed: 28161477
PLoS One. 2014 Aug 13;9(8):e104306
pubmed: 25119879
Adv Drug Deliv Rev. 1999 Apr 5;36(2-3):165-178
pubmed: 10837714
Semin Hematol. 2016 Apr;53 Suppl 1:S54-7
pubmed: 27312167
J Cereb Blood Flow Metab. 2017 Aug;37(8):2894-2909
pubmed: 28273717
Lab Invest. 2019 Jul;99(8):1245-1255
pubmed: 30996296
Virus Res. 2012 Dec;170(1-2):66-74
pubmed: 23000117
J Immunol. 2014 Sep 1;193(5):2427-37
pubmed: 25063869
Nat Rev Immunol. 2012 Sep;12(9):623-35
pubmed: 22903150
Nat Immunol. 2011 Dec 04;13(1):67-76
pubmed: 22138716
Annu Rev Immunol. 2016 May 20;34:317-34
pubmed: 27168241
Pharm Res. 2015 Sep;32(9):2973-82
pubmed: 25986174
Front Cell Neurosci. 2012 Aug 09;6:33
pubmed: 22907989
Immunol Rev. 2012 Jul;248(1):205-15
pubmed: 22725963
J Neuroinflammation. 2019 Nov 21;16(1):232
pubmed: 31752904
Nat Immunol. 2007 Jun;8(6):639-46
pubmed: 17486092
J Cereb Blood Flow Metab. 2019 Mar;39(3):395-410
pubmed: 30565961
Mucosal Immunol. 2016 Sep;9(5):1151-62
pubmed: 26732677
Brain. 2018 May 1;141(5):1334-1349
pubmed: 29659729
Nature. 1985 Apr 11-17;314(6011):537-9
pubmed: 3157869
Nat Rev Immunol. 2003 Jul;3(7):569-81
pubmed: 12876559
Tissue Barriers. 2015 Apr 03;3(1-2):e969100
pubmed: 25838976
J Immunol. 2012 Oct 1;189(7):3618-30
pubmed: 22942431
Fluids Barriers CNS. 2016 Jan 29;13:2
pubmed: 26833402
Brain. 2009 Dec;132(Pt 12):3329-41
pubmed: 19933767
PLoS One. 2014 Jun 17;9(6):e99733
pubmed: 24936790
Neurology. 2012 Feb 14;78(7):458-67; discussion 465
pubmed: 22302546
Nature. 2012 Apr 26;484(7395):514-8
pubmed: 22466287