2012 Fiscal Year Final Research Report
Analysis of PI3K signaling role in regulatory B cells
| Project/Area Number |
23791260
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | 制御性B細胞 IL-10 / 自己免疫疾患 |
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| Research Abstract |
IL-10 producing regulatory B (Breg) cells negatively regulates autoimmune disease and inflammation, such as contact hypersensitivity (CHS). CD19 expression is critical for Breg cells development, since CD19 loss results in decreased number of Breg cell and increased reactivity of CHS. However, molecular mechanism of Breg cell development remains poorly understood. CD19 downstream signal is depend on the activation of phosphoinositide 3-kinases (PI3K)-AKT pathways, while phosphatase and tensin homologue (PTEN) attenuates PI3K-AKT pathways. In this study, we investigated the role of PI3K-AKT pathway in the development of Breg cells. The effect of PI3K-AKT pathway inhibitors on Breg cell development was examined in vitro. B cell-specific PTEN deficient mice, which exhibit aberrant activation of PI3K-AKT pathway in B cell, were generated using Cre-loxp system. CHS severity in B cell-specific PTEN deficient mice was investigated. The current studies demonstrate that PI3K-AKT pathway inhibitors reduced Breg cells in vitro in dose-dependent manner. However, PTEN inhibitor had no effect on Breg cells. Breg cell number and frequency were significantly increased in various organs of B cell-specific PTEN deficient mice when compared with wild-type mice. Furthermore, CHS response was significantly diminished in B cell-specific PTEN deficient mice when compared with wild-type mice. Thus, PI3K-AKTpathway positively regulates Breg cell development, while PTEN negatively regulates it. PI3K-AKT pathway in B cell is critical for Breg cell development and could be a potent therapeutical target.
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Author(s)
Fujimoto M, Matsushita T, Hamaguchi Y, Kaji K, Asano Y, Ogawa F, Yamaoka T, Fujikawa K, Tsukada T, Sato K, Echigo T, Hasegawa M, Takehara K
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Journal Title
Ann Rheum Dis
Volume: 72
Pages: 151-3
DOI
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[Journal Article] haracterization of a Rare IL-10-Competent B Cell Subset in Man That Parallels Mouse Regulatory B10 Cells2011
Author(s)
Iwata Y*, Matsushita T*, Horikawa, DiLillo, Yanaba, Venturi, Szabolcs, Bernstein, Magro, Williams, Hall, St.Clair, and Tedder TF
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Journal Title
Blood
Volume: 117
Pages: 530-41
DOI
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