| Project/Area Number |
26253029
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OHTEKI Toshiaki 東京医科歯科大学, 難治疾患研究所, 教授 (50233200)
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| Co-Investigator(Renkei-kenkyūsha) |
ONAI Nobuyuki 東京医科歯科大学, 難治疾患研究所, 講師 (50323605)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥40,300,000 (Direct Cost: ¥31,000,000、Indirect Cost: ¥9,300,000)
Fiscal Year 2016: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2015: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2014: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
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| Keywords | 樹状細胞 / E2-2 / pDC / cDC / CDP / CD103陽性cDC / Treg / 免疫寛容 / 分化転換 / ALDH / 免疫学 / 組織・細胞 / 生体分子 / IRF8 / 樹状細胞（DC） / DC前駆細胞（CDP） / 従来型DC（cDC） / 形質細胞様DC（pDC） / CDPニッチ |
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| Outline of Final Research Achievements |
Transcription factor E2-2 is essential for the development of plasmacytoid dendritic cells (pDCs) but not conventional DCs (cDCs). In this study, we generated E2-2 reporter mice and demonstrated that an E2-2high fraction among common DC progenitors (CDPs) strictly gave rise to pDCs in the presence of Flt3 ligand ex vivo or in the secondary lymphoid organs when transferred in vivo. However, in the small intestine, some of these E2-2high progenitors differentiated into cDCs that produced retinoic acid. This transdifferentiation was driven by signaling via the common β receptor, a receptor for the cytokines IL-3, IL-5 and GM-CSF, which are abundant in the gut. In the presence of GM-CSF and Flt3 ligand, E2-2high-progenitor-derived cDCs consistently induced Foxp3+ regulatory T cells ex vivo. Our findings reveal the commitment and flexibility of E2-2high progenitor differentiation, and imply that pertinent tuning machinery is present in the gut microenvironment.
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