C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE

Reboldi, Andrea; Coisne, Caroline; Baumjohann, Dirk; Benvenuto, Federica; Bottinelli, Denise; Lira, Sergio; Uccelli, Antonio; Lanzavecchia, Antonio; Engelhardt, Britta; Sallusto, Federica (2009). C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nature immunology, 10(5), pp. 514-23. New York, N.Y.: Nature Publishing Group 10.1038/ni.1716

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Interleukin 17-producing T helper cells (T(H)-17 cells) are important in experimental autoimmune encephalomyelitis, but their route of entry into the central nervous system (CNS) and their contribution relative to that of other effector T cells remain to be determined. Here we found that mice lacking CCR6, a chemokine receptor characteristic of T(H)-17 cells, developed T(H)-17 responses but were highly resistant to the induction of experimental autoimmune encephalomyelitis. Disease susceptibility was reconstituted by transfer of wild-type T cells that entered into the CNS before disease onset and triggered massive CCR6-independent recruitment of effector T cells across activated parenchymal vessels. The CCR6 ligand CCL20 was constitutively expressed in epithelial cells of choroid plexus in mice and humans. Our results identify distinct molecular requirements and ports of lymphocyte entry into uninflamed versus inflamed CNS and suggest that the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Coisne, Caroline Marie, Engelhardt, Britta

ISSN:

1529-2908

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

05 Dec 2022 14:22

Publisher DOI:

10.1038/ni.1716

PubMed ID:

19305396

Web of Science ID:

000265394400013

URI:

https://boris.unibe.ch/id/eprint/32145 (FactScience: 197072)

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