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

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K20949
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Collagenous pathology/Allergology
• Research Institution: The 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
• Keywords: 慢性肉芽腫 / autoinflammation / intestine organoid

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.

Free Research Field

造血幹細胞、幹細胞生物学