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  T cells become licensed in the lung to enter the central nervous system

Odoardi, F., Sie, C., Streyl, K., Ulaganathan, V. K., Schlaeger, C., Lodygin, D., et al. (2012). T cells become licensed in the lung to enter the central nervous system. NATURE, 488(7413), 675-679. doi:10.1038/nature11337.

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Odoardi, Francesca1, Author              
Sie, Christopher1, Author
Streyl, Kristina2, Author              
Ulaganathan, Vijay Kumar2, Author              
Schlaeger, Christian1, Author
Lodygin, Dmitri1, Author
Heckelsmiller, Klaus2, Author              
Nietfeld, Wilfried3, Author              
Ellwart, Joachim1, Author
Klinkert, Wolfgang E. F.2, Author              
Lottaz, Claudio1, Author
Nosov, Mikhail1, Author              
Brinkmann, Volker1, Author              
Spang, Rainer4, Author              
Lehrach, Hans3, Author              
Vingron, Martin4, Author              
Wekerle, Hartmut2, Author              
Fluegel-Koch, Cassandra1, Author
Fluegel, Alexander1, Author
Affiliations:
1external, ou_persistent22              
2Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              
3Dept. of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
4Dept. of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              

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Free keywords: EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; ADHESION MOLECULE; MICROARRAY DATA; MYELOID CELLS; LYMPHOCYTES; MIGRATION; ANTIGEN; CNS; INFECTIONS
 Abstract: The blood-brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB1,2 and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma(3-6). Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. Instead, intravenously transferred T-cell blasts gain the capacity to enter the CNS after residing transiently within the lung tissues. Inside the lung tissues, they move along and within the airways to bronchus-associated lymphoid tissues and lung-draining mediastinal lymph nodes before they enter the blood circulation from where they reach the CNS. Effector T cells transferred directly into the airways showed a similar migratory pattern and retained their full pathogenicity. On their way the T cells fundamentally reprogrammed their gene-expression profile, characterized by downregulation of their activation program and upregulation of cellular locomotion molecules together with chemokine and adhesion receptors. The adhesion receptors include ninjurin 1, which participates in T-cell intravascular crawling on cerebral blood vessels. We detected that the lung constitutes a niche not only for activated T cells but also for resting myelin-reactive memory T cells. After local stimulation in the lung, these cells strongly proliferate and, after assuming migratory properties, enter the CNS and induce paralytic disease. The lung could therefore contribute to the activation of potentially autoaggressive T cells and their transition to a migratory mode as a prerequisite to entering their target tissues and inducing autoimmune disease.

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Language(s): eng - English
 Dates: 2012-08-30
 Publication Status: Published in print
 Pages: 5
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000308095100060
DOI: 10.1038/nature11337
 Degree: -

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Title: NATURE
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 488 (7413) Sequence Number: - Start / End Page: 675 - 679 Identifier: ISSN: 0028-0836