Transcriptional regulation of CCR10 expression in plasma cells
| Project/Area Number |
17590443
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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 | Kinki Univeristy |
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Principal Investigator |
YOSHIE Osamu Kinki Univeristy, School of Medicine, Professor, 医学部, 教授 (10166910)
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| Co-Investigator(Kenkyū-buntansha) |
HIESHIMA Kunio Kinki Univeristy, School of Medicine, Lecturer, 医学部, 講師 (10322570)
NAKAYAMA Takashi Kinki Univeristy, School of Medicine, Lecturer, 医学部, 講師 (60319663)
NAGAKUBO Daisuke Kinki Univeristy, School of Medicine, Assistant, 医学部, 助手 (10368293)
SHIRAKAWA Aiko-konno Kinki Univeristy, School of Medicine, Assistant, 医学部, 助手 (30260285)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | plasma cell / CCR10 / mucosal immunity / transcription factor / IL-21 / vitamin D / Ets-1 / Vitamin D3 receptor / ケモカインレセプター / プローモーター / Ets / Ikaros |
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| Research Abstract |
CCR10 has been reported to be expressed by almost all IgA-secreting plasma cells, while its ligand CCL28 is widely expressed in various mucosal tissues. Thus, the CCR10-CCL28 system is likely to contribute a wide distribution of IgA-secreting plasma cells in the common mucosal immune system. Here we examined the mechanism of CCR10 expression in terminally differentiating B cells. As reported previously, activated human CD19^+ B cells treated with IL-21 efficiently differentiated into IgD^-CD38^+ plasma cells. Even though IgD^-CD38^+ cells did not spontaneously expressed CCR10, a substantial fraction turned to express CCR10 if the differentiation was induced in the presence of 1,25-dihydroxyvitamin D3 (1,25-(OH)_2D_3), which is known to promote common mucosal immune responses if used as an adjuvant. However, we observed little increases in IgA^+ cells by 1,25-(OH)_2D_3. To determine the transcriptional mechanism regulating 1,25-(OH)_2D_3-inducible expression of CCR10 in terminally differentiating B cells, we next carried out a series of analysis on the CCR10 promoter. The reporter assays involving a series of 5'-deleted promoter fragments and promoter fragments with site-directed mutations revealed that a proximal Ets-1 site and an upstream vitamin D3 response element (VDRE) were critical for CCR10 expression. The NoShift transcription factor binding assays using nuclear extracts from CCR10-expressing myeloma cell lines confirmed specific binding of Ets-1 and 1,25-(OH)_2D_3-activated vitamin D3 receptor (VDR) to the respective elements. Collectively, 1,25-(OH)2D3 efficiently induces CCR10 expression in IL-21-induced human plasma cells in vitro. Furthermore, the CCR10 promoter is cooperatively activated by 1,25-(OH)_2D_3-activated VDR and Ets-1.
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Report
(3 results)
Research Products
(1 results)
