2007 Fiscal Year Final Research Report Summary
Identification of transcription factors that control memory Th2 cell differentiation
| Project/Area Number |
18590466
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Chiba University |
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Principal Investigator |
YAMASHITA Masakatsu Chiba University, Graduate School of Medicine, Associate Professor (00311605)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Memory Th2 cells / Transcription factors / Allergy / MLL / Bmi1 / Noxa / Gfi1 / GATA3 |
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| Research Abstract |
One of the difficulties in memory Th2 cell study is limited numbers of antigen-specific memory Th2 cell in vivo. We developed an adoptive transfer technique for the generation of large number of antigen-specific memory Th2 cell in vivo. Using this technique, we tried to identify transcription factors, which are important for memory Th2 cell differentiation.
The following results could be achieved for this research on two years. (1) Mixed lineage leukemia (MLL) is required for the maintenance of Th2 cell identity in memory Th2 cells (Yamashita, et. Al. Immunity 24: 611, 2006). MLL appears to regulate stable Th2 identity through the epigenetic control of the GATA3 locus and the Th2 cytokine gene loci in memory Th2 cells. (2) Bmi1, a member of polycomb gene family, is required for proper generation of memory Th2 cells (Yamashita, et. Al., J. Exp. Med. 2008, in press). In the absence of Bmi1, the generation of Th2 memory cells was impaired as a consequence of increased Noxa expression. Our results indicate that Bmi1 controls memory Th2 cell survival and function through the direct repression of the Noxa gene. (3) Gfi1, a member of C2H2 type zinc finger transcription factors, is important for the stabilization of Th2 cell identity. Gfi1-mediated stabilization of GATA3 protein is required for the establishment of Th2 cell identity (Shinnakasu, et. Al., in preparation).
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