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

Garnier, Arnaud; Laffont, Sophie; Garnier, Laure; Kaba, Elisa; Deutsch, Urban; Engelhardt, Britta; Guéry, Jean-Charles (2019). CD49d/CD29-integrin controls the accumulation of plasmacytoid dendritic cells into the CNS during neuroinflammation. European journal of immunology, 49(11), pp. 2030-2043. Wiley-VCH 10.1002/eji.201948086

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

UniBE Contributor:

Kaba, Elisa; Deutsch, Urban and Engelhardt, Britta

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0014-2980

Publisher:

Wiley-VCH

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

13 Nov 2019 09:24

Last Modified:

15 Nov 2019 01:33

Publisher DOI:

10.1002/eji.201948086

PubMed ID:

31318439

Uncontrolled Keywords:

CD29 integrins CNS autoimmunity cell trafficking innate immunity plasmacytoid dendritic cells

BORIS DOI:

10.7892/boris.134679

URI:

https://boris.unibe.ch/id/eprint/134679

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