Mechanism of autoinflammation in chronic granulomatous disease: the molecular crosstalk between innate immune cells and gastrointestinal environments
| Project/Area Number |
15K20949
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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 |
Pediatrics
Collagenous pathology/Allergology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Lai Chen-Yi 東京大学, 医科学研究所, 特任助教 (30739925)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 慢性肉芽腫 / autoinflammation / intestine organoid / Autoinflammation / CGD |
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| Outline of Final Research Achievements |
Chronic granulomatous disease (CGD) is a phagocyte disorder. It is also characterized by autoinflammation in the gastrointestinal (GI) tract, where innate lymphoid cells (ILCs) reside. Here, we clarified that the hematopoietic stem and progenitor cells, the origin of ILCs, in the CGD mice are comparable to wild-type control. Induced pluripotent stem (iPS) cells were generated from CGD patients. The human intestinal organoids (HIOs) were successfully generated from iPS cells. The resulting HIOs showed structures resembled normal morphology of human intestines and could be expanded more than 4 months suggesting the maintenance of the self-renewability of intestine stem cells. This is the first successful attempt at generating intestinal tissue from CGD-iPS cells. This is of importance due to the availability of patient’s samples and existing discrepancies between species. Here we established a new platform for studying human GI system in vitro and the pathophysiology of CGD colitis.
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Report
(3 results)
Research Products
(3 results)
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[Journal Article] Pre-Transplantation Blockade of TNF-α-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells.2017
Author(s)
Ishida T, Suzuki S, Lai CY, Yamazaki S, Kakuta S, Iwakura Y, Nojima M, Takeuchi Y, Higashihara M, Nakauchi H, Otsu M.
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Journal Title
Stem Cells.
Volume: 35
Issue: 4
Pages: 989-1002
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 1.An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.2017
Author(s)
Ieyasu A, Ishida R, Kimura T, Morita M, Wilkinson AC, Sudo K, Nishimura T, Ohehara J, Tajima Y, Lai CY, Otsu M, Nakamura Y, Ema H, Nakauchi H, Yamazaki S
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Journal Title
Stem Cell Reports
Volume: 14
Issue: 3
Pages: 500-508
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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