CD49d/CD29-integrin controls the accumulation of plasmacytoid dendritic cells into the CNS during neuroinflammation.
Adoptive Transfer
Animals
Brain
/ drug effects
Cell Movement
/ immunology
Dendritic Cells
/ drug effects
Encephalomyelitis, Autoimmune, Experimental
/ chemically induced
Female
Gene Expression Regulation
Immunity, Innate
Integrin alpha4
/ genetics
Integrin beta1
/ genetics
Interferon Regulatory Factor-7
/ genetics
Interferon Type I
/ genetics
Interleukin-12 Subunit p40
/ genetics
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein
/ administration & dosage
Peptide Fragments
/ administration & dosage
Pertussis Toxin
/ administration & dosage
Signal Transduction
Spinal Cord
/ drug effects
Toll-Like Receptor 9
/ genetics
CD29 integrins
CNS autoimmunity
cell trafficking
innate immunity
plasmacytoid dendritic cells
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
04
01
2019
revised:
28
05
2019
accepted:
16
07
2019
pubmed:
19
7
2019
medline:
27
5
2020
entrez:
19
7
2019
Statut:
ppublish
Résumé
Plasmacytoid dendritic cells (pDCs) are found in the CNS during neuroinflammation and have been reported to exert regulatory functions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms of entry of pDCs into the CNS as well as their phenotype and innate functional properties, once recruited into the CNS, have not been thoroughly examined. Herein, we show that pDCs rapidly accumulate into the brain and spinal cord during the acute phase of EAE, and maintain the expression of numerous phenotypic markers typical of peripheral pDCs. Functionally, CNS-pDCs constitutively expressed IRF7 and were able to rapidly produce type I IFNs and IL-12p40 upon ex vivo TLR-9 stimulation. Using adoptive transfer experiments, we provide evidence that CNS-pDC are recruited from the blood and accumulate into the CNS during the acute phase of EAE. Accumulation of pDCs into the CNS was strongly inhibited in the absence of CD29, but not CD18, suggesting a major role for ß1 but not ß2 integrins. Indeed, blocking the CD49d α4-integrins during acute EAE drastically diminished CNS-pDC numbers. Together, our results demonstrate that circulating pDCs are actively recruited into the CNS during acute EAE through a mechanism largely dependent on CD49d/CD29-integrins.
Identifiants
pubmed: 31318439
doi: 10.1002/eji.201948086
doi:
Substances chimiques
Integrin beta1
0
Interferon Regulatory Factor-7
0
Interferon Type I
0
Interleukin-12 Subunit p40
0
Irf7 protein, mouse
0
Itgb1 protein, mouse
0
Myelin-Oligodendrocyte Glycoprotein
0
Peptide Fragments
0
Tlr9 protein, mouse
0
Toll-Like Receptor 9
0
myelin oligodendrocyte glycoprotein (35-55)
0
Integrin alpha4
143198-26-9
Pertussis Toxin
EC 2.4.2.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2030-2043Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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