期刊
ELIFE
卷 6, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.25517
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资金
- Japan Society for the Promotion of Science [KAKENHI 15K19122]
- Takeda Science Foundation
- Institute for Fermentation, Osaka
- Mitsubishi Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Suzuken Memorial Foundation
- Japan Prize Foundation
- Kishimoto Foundation
- Nagao Takeshi Research Foundation
- Japan Multiple Sclerosis Society
- Kanae Foundation for the Promotion of Medical Science
- Tokyo Medical Research Foundation
- Japan Society for the Promotion of Science
- Ono Medical Research Foundation
- Kanzawa Medical Reseach Foundation
- Uehara Memorial Foundation
- Japan Brain Foundation
- Kao Foundation for Arts and Sciences
- Japan Society for the Promotion of Science KAKENHI [15H04741, 15K08518]
- Grants-in-Aid for Scientific Research [15K08518, 15H04741, 16H01849, 17K19537] Funding Source: KAKEN
Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-ofhypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis.
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