Elucidation of maintenance mechanism of intestinal homeostasis through control of small intestinal epithelial lymphocytes by Notch signal
| Project/Area Number |
15K19131
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ISHIFUNE Chieko 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (80632645)
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| Co-Investigator(Renkei-kenkyūsha) |
YASUTOMO Koji 徳島大学, 大学院医歯薬学研究部, 教授 (30333511)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Notchシグナル / 上皮間リンパ球 / フリッパーセ / マクロファージ / フリッパーゼ / 腸管上皮間リンパ球 |
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| Outline of Final Research Achievements |
We demonstrated in this study that Notch1, 2 and Rbpj-mediated Notch signal controls the number and maturation of TCRαβ+CD8αα+ (CD8αα) intraepithelial lymphocyte (IEL), one of four major IEL subsets, in the small intestine. The analysis using bone marrow chimeric mice revealed that intrinsic Notch signal in CD8αα IEL at intraepithelial stage is required for maintaining the number of CD8αα IEL. By DNA microarray analysis, we identified Atp8a2 as one of Notch target genes in CD8αα IEL. As Atp8a2 has flippase activity, Rbpj deficient CD8αα IEL exhibited lower flippase activity than control cells. The depletion of intestinal macrophages by administrating anit-CSF1 receptor antibody in T cell specific Rbpj deficient mice increased the number of CD8αα IEL in the small intestine. Our data suggest that Notch-mediated Atp8a2 expression modulates the number of CD8αα IEL through control of phospholipid asymmetry and engulfment of macrophages.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Regulation of monocyte cell fate by blood vessels mediated by Notch signalling2016
Author(s)
Gamrekelashvili J, Giagnorio R, Jussofie J, Soehnlein O, Duchene J, Briseno CG, Ramasamy SK, Krishnasamy K, Limbourg A, Kapanadze T, Ishifune C, Hinkel R, Radtke F, Strobl LJ, Zimber-Strobl U, Napp LC, Bauersachs J, Haller H, Yasutomo K, Kupatt C, Murphy KM, Adams RH, Weber C, Limbourg FP
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Journal Title
Nature Communications
Volume: 7
Issue: 1
Pages: 12597
DOI
NAID
URL
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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