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Mechanism of autoinflammation in chronic granulomatous disease: the molecular crosstalk between innate immune cells and gastrointestinal environments

Research Project

Project/Area Number 15K20949
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Collagenous pathology/Allergology
Research InstitutionThe University of Tokyo

Principal Investigator

Lai Chen-Yi  東京大学, 医科学研究所, 特任助教 (30739925)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
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)
Keywords慢性肉芽腫 / autoinflammation / intestine organoid / Autoinflammation / CGD
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.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (3 results)

All 2017 2015

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (1 results)

  • [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.
    • Journal Title

      Stem Cells.

      Volume: 35 Issue: 4 Pages: 989-1002

    • DOI

      10.1002/stem.2524

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Stem Cell Reports

      Volume: 14 Issue: 3 Pages: 500-508

    • DOI

      10.1016/j.stemcr.2017.01.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Roles for Cxcr4 signaling in murine hematopoietic stem/progenitor cells in bone marrow repopulation2015

    • Author(s)
      Chen-Yi Lai
    • Organizer
      第80回日本インターフェロン・サイトカイン学会
    • Place of Presentation
      東京工業大学蔵前会館(東京都目黒区)
    • Year and Date
      2015-07-17
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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