CD49d/CD29-integrin controls the accumulation of plasmacytoid dendritic cells into the CNS during neuroinflammation

Arnaud Garnier; Sophie Laffont; Laure Garnier; Elisa Kaba; Urban Deutsch; Britta Engelhardt; Jean-Charles Guéry

doi:10.1002/eji.201948086

CD49d/CD29-integrin controls the accumulation of plasmacytoid dendritic cells into the CNS during neuroinflammation

Eur J Immunol. 2019 Nov;49(11):2030-2043. doi: 10.1002/eji.201948086. Epub 2019 Jul 26.

Authors

Arnaud Garnier¹, Sophie Laffont¹, Laure Garnier¹, Elisa Kaba², Urban Deutsch², Britta Engelhardt², Jean-Charles Guéry¹

Affiliations

¹ Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, INSERM, CNRS, UPS, Toulouse, France.
² Theodor Kocher Institute, University of Bern, Bern, Switzerland.

PMID: 31318439
DOI: 10.1002/eji.201948086

Abstract

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.

Keywords: CD29 integrins; CNS autoimmunity; cell trafficking; innate immunity; plasmacytoid dendritic cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
Brain / drug effects
Brain / immunology*
Brain / pathology
Cell Movement / immunology
Dendritic Cells / drug effects
Dendritic Cells / immunology*
Dendritic Cells / pathology
Dendritic Cells / transplantation
Encephalomyelitis, Autoimmune, Experimental / chemically induced
Encephalomyelitis, Autoimmune, Experimental / genetics
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / pathology
Female
Gene Expression Regulation
Immunity, Innate
Integrin alpha4 / genetics
Integrin alpha4 / immunology*
Integrin beta1 / genetics
Integrin beta1 / immunology*
Interferon Regulatory Factor-7 / genetics
Interferon Regulatory Factor-7 / immunology
Interferon Type I / genetics
Interferon Type I / immunology
Interleukin-12 Subunit p40 / genetics
Interleukin-12 Subunit p40 / immunology
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein / administration & dosage
Peptide Fragments / administration & dosage
Pertussis Toxin / administration & dosage
Signal Transduction
Spinal Cord / drug effects
Spinal Cord / immunology*
Spinal Cord / pathology
Toll-Like Receptor 9 / genetics
Toll-Like Receptor 9 / immunology

Substances

Integrin beta1
Interferon Regulatory Factor-7
Interferon Type I
Interleukin-12 Subunit p40
Irf7 protein, mouse
Itgb1 protein, mouse
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments
Tlr9 protein, mouse
Toll-Like Receptor 9
myelin oligodendrocyte glycoprotein (35-55)
Integrin alpha4
Pertussis Toxin