Comprehensive understanding of dendritic cell progenitor and its therapeutic application basis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253029
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OHTEKI Toshiaki 東京医科歯科大学, 難治疾患研究所, 教授 (50233200)
• Co-Investigator(Renkei-kenkyūsha): ONAI Nobuyuki 東京医科歯科大学, 難治疾患研究所, 講師 (50323605)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 樹状細胞 / E2-2 / pDC / cDC / CDP / CD103陽性cDC / Treg / 免疫寛容

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.

Free Research Field

免疫学