| Project/Area Number |
26893231
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Osaka City University |
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Principal Investigator |
Hosomi Shuhei 大阪市立大学, 大学院医学研究科, 病院講師 (60554938)
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| Research Collaborator |
Blumberg Richard S. Brigham and Women's Hospital, Harvard Medical school
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 炎症性腸疾患 / 腸管免疫 / 小胞体ストレス / NKG2D |
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| Outline of Final Research Achievements |
Endoplasmic reticulum stress (ER stress) is commonly observed in intestinal epithelial cells (IEC) and can be a primary factor in intestinal inflammation as shown by mice with IEC-specific deletion of X-box binding protein-1 (Xbp1), an unfolded protein response-related transcription factor, which develop spontaneous inflammation of the small intestine. In the present study, I showed that ER -stressed IECs, as a consequence of Xbp1 deletion, selectively upregulate mouse NKG2D-ligand MULT1 and its human orthologue ULBP through ER stress-related transcription factor CHOP. The increased expression of NKG2D-ligand on mouse IECs induces and activates intraepithelial natural killer (NK) cells through their expression of NKG2D. The ULBPs expression was induced by ER stress in not only intestinal cell line but also other cell lines, indicating that the NKG2D-ligands induction by ER stress might be universal phenomenon to maintain homeostasis in our body.
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