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题目:: A novel splenic B1 regulatory cell subset suppresses allergic disease through phosphatidylinositol 3-kinase-Akt pathway activation.
作者:: Matsushita(Takashi),Le Huu(Doanh),Kobayashi(Tadahiro),Hamaguchi(Yasuhito),Hasegawa(Minoru),Naka(Kazuhito),Hirao(Atsushi),Muramatsu(Masamichi),Takehara(Kazuhiko),Fujimoto(Manabu)
状态:: 发布时间2016-03-07 , 更新时间 2016-10-10
期刊:: J Allergy Clin Immunol
摘要:: IL-10-producing regulatory B (B10) cells potently suppress allergic diseases, such as contact hypersensitivity (CHS). Splenic B10 cells share overlapping phenotypic markers with CD5 B1 B cells, CD1dCD21CD23 marginal zone (MZ) B cells, and CD1dCD21CD23 T2-MZ precursor B cells but do not exclusively belong to either subset.,In this study we investigated the signaling mechanisms and a novel phenotypic parameter of B10 cells.,We performed microarray analysis comparing IL-10 and IL-10 B cells. B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice, which exhibit aberrant activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway in B cells, were examined.,Microarray analysis revealed that the PI3K-Akt pathway is important for IL-10 production in B cells. PI3K-Akt pathway inhibitors reduced B10 cell numbers in vitro. B10 cell numbers were significantly increased in B cell-specific PTEN-deficient mice. The CHS response was significantly diminished in PTEN-deficient mice. Unexpectedly, splenic B10 cells in these mice were found within the B1 B-cell subset but not within the MZ B-cell subset. In wild-type mice not only MZ B10 cells but also B1-B10 cells were identified in the spleen. In addition, these 2 B10 cell subsets were predominantly found within the CD9CD80 B-cell fraction.,A novel splenic B1 regulatory cell subset (B1-B10 cells) was identified. Our findings show that the PI3K-Akt pathway in B cells is critical for B10 cell development and CHS response and that CD9/CD80 coexpression is a novel phenotypic parameter for both MZ-B10 and B1-B10 cells.
语言:: eng
DOI:: 10.1016/j.jaci.2015.12.1319

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