Regulation of intestinal and hepatic immunity by vitamin D receptor signaling
| Project/Area Number |
16K08632
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | ビタミンD受容体 / 肝障害 / 炎症 / Kupffer細胞 / 活性酸素種 / 貪食能 / 胆汁酸 / ビタミンD誘導体 / 肝炎 / ケノデオキシコール酸 / リトコール酸 / 大腸炎 / 核内受容体 / NKT細胞 / サイトカイン / 免疫学 / 栄養学 / 脂質 / シグナル伝達 / 生理活性 |
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| Outline of Final Research Achievements |
We investigated the non-calcemic roles of vitamin D receptor (VDR) signaling in the liver and intestine, specifically in hepatic immune cells. Decreased levels of reactive oxygen species and decreased phagocytic activity in hepatic immune cells, such as resident Kupffer cells, were involved in attenuated concanavalin-A-induced acute hepatitis in VDR-knockout mice, indicating that VDR plays a role in hepatic immune functions. Oral administration of 1,25(OH)2D3 induced VDR target gene expression effectively in the duodenum and jejunum, and lithocholic acid administration increased target gene expression selectively in the ileum. VDR deletion decreased urinary bile acid excretion and increased plasma bile acid levels in mice fed a chow supplemented with chenodeoxycholic acid. Thus, VDR signaling regulates hepatic and intestinal functions, including immunity and bile acid metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
VDRの非カルシウム作用として炎症抑制作用が知られているが、我々の研究成果は、VDRが常在性Kupffer細胞などの肝臓免疫細胞の機能発現に重要であることを初めて示したものである。ビタミンDの不足状態は、B型及びC型ウイルス性肝炎の増悪因子だが、我々の示したVDRの自然免疫機能の関与が考えられる。また、リトコール酸が下部小腸選択的にVDRに作用し、VDR欠損は胆汁酸代謝に影響を与えるとの知見は、胆汁酸-VDRシグナルを介した腸内細菌と生体の相互作用を裏付けるものである。腸管・肝臓におけるビタミンD/胆汁酸-VDRシグナリングの研究成果は、生活習慣病や免疫疾患の病態の解明へ応用できる。
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Dual conformation of the ligand induces the partial agonistic activity of retinoid X receptor α (RXRα)2018
Author(s)
Yurina Miyashita, Nobutaka Numoto, Sundaram Arulmozhiraja, Shogo Nakano, Naoya Matsuo, Kanade Shimizu, Osamu Shibahara, Michiko Fujiwara, Hiroki Kakuta, Sohei Ito, Teikichi Ikura, Nobutoshi Ito, Hiroaki Tokiwa
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Journal Title
FEBS Letters
Volume: 593(2)
Issue: 15
Pages: 242-250
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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