期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-38895-y
关键词
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资金
- KAKENHI
- Joint Usage/Research Center Institute for Genetic Medicine, Hokkaido University
- JSPS Postdoctoral Fellowship for Foreign Researchers
- Takeda Science Foundation
- Institute for Fermentation Osaka
- Mitsubishi Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Suzuken Memorial Foundation
- Japan Prize Foundation
- Ono Medical Research Foundation
- Kanzawa Medical Research Foundation
- Kishimoto Foundation
- Nagao Takeshi Research Foundation
- Japan Multiple Sclerosis Society
- Kanae Foundation
- Tokyo Medical Research Foundation
- Progres Q35
- Uehara Memorial Foundation
- Japan Brain Foundation
- Kao Foundation
- Suhara Memorial Foundation
- Yasuda Memorial Foundation
- Novartis Pharma Research Grants
- [GACR 18-11795Y]
- [PRIMUS/17/MED/7]
We have reported the gateway reflex, which describes specific neural activations that regulate immune cell gateways at specific blood vessels in the central nervous system (CNS). Four types of gateway reflexes exist, all of which induce alterations in endothelial cells at specific vessels of the blood-brain barrier followed by inflammation in the CNS in the presence of CNS-autoreactive T cells. Here we report a new gateway reflex that suppresses the development of retinal inflammation by using an autoreactive T cell-mediated ocular inflammation model. Exposure to photopic light down-regulated the adrenoceptor pathway to attenuate ocular inflammation by suppressing breaching of the blood-retina barrier. Mechanistic analysis showed that exposure to photopic light down-regulates the expression of alpha(1A)-adrenoceptor (alpha(1A)AR) due to high levels of norepinephrine and epinephrine, subsequently suppressing inflammation. Surgical ablation of the superior cervical ganglion (SCG) did not negate the protective effect of photopic light, suggesting the involvement of retinal noradrenergic neurons rather than sympathetic neurons from the SCG. Blockade of alpha(1A)AR signaling under mesopic light recapitulated the protective effect of photopic light. Thus, targeting regional adrenoceptor signaling might represent a novel therapeutic strategy for autoimmune diseases including those that affect organs separated by barriers such as the CNS and eyes.
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