| Item type: | Article | ||||||||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | Nature | ||||||||||||||||||||||||||||||||||||||||
| Publisher: | Nature Publishing Group | ||||||||||||||||||||||||||||||||||||||||
| Volume: | 488 | ||||||||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 7413 | ||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 675-679 | ||||||||||||||||||||||||||||||||||||||||
| Date: | August 2012 | ||||||||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatics and Data Science > Department Computational Life Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) | ||||||||||||||||||||||||||||||||||||||||
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| Classification: |
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| Dewey Decimal Classification: | 500 Science > 500 Natural sciences & mathematics 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Partially | ||||||||||||||||||||||||||||||||||||||||
| Item ID: | 30594 |
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 BBB and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels ...
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 BBB 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. 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.
Metadata last modified: 03 Mar 2022 10:17
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