Identification of transcription factors responsible for suppression of dendritic cells by regulatory T cells and development of immunotherapy

鉴定负责调节性 T 细胞抑制树突状细胞的转录因子并开发免疫疗法

• 批准号: 23791067
• 负责人: ONISHI Yasushi
• 金额: $ 2.75万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791067/
• 关键词: 樹状細胞; 免疫寛容; 制御性T細胞; ＦｏｘＯ３ａ; ＣＤ８６; 免疫療法; 移植再生医療; FoxO3a; ＣＤ86; TIM-3; CD86; 免疫学; 移植・再生医療; CTLA-4

Suppression of FoxO3a in human monocyte-derived dendritic cells (DC) increased the expression of CD80/86 and HLA-DR. T-cell proliferation and production of inflammatory cytokines, IL-6 and TNFa, were enhanced in co-culture of FoxO3a-knockdown DC and T cells. The activation of DC by FoxO3a suppression was dependent on NF-kB. When DC was stimulated with LPS, FoxO3a was promptly phosphorylated and moved to cytoplasm from nucleus. Levels of FoxO3a mRNA increased later than elevation of CD86 mRNA levels after the addition of LPS. Inactivation of FoxO3a induced the activation of DC in an early phase of the LPS stimulation. These results suggest that FoxO3a has a central role in the regulation of DC functions.

在人单核细胞来源的树突状细胞（DC）中FoxO 3a的抑制增加了CD 80/86和HLA-DR的表达。在FoxO 3a敲低的DC和T细胞的共培养中，T细胞增殖和炎性细胞因子IL-6和TNFa的产生增强。FoxO 3a抑制对DC的激活依赖于NF-κ B。当用LPS刺激DC时，FoxO 3a迅速磷酸化并从细胞核移动到细胞质。加入LPS后，FoxO 3a mRNA水平的升高晚于CD 86 mRNA水平的升高。FoxO 3a的失活在LPS刺激的早期阶段诱导DC的活化。这些结果表明FoxO 3a在DC功能的调节中具有核心作用。

项目成果

Addition of oral cyclophosphamide is effective for myeloma refractory to lenalidomide/dexamethasone

加用口服环磷酰胺对来那度胺/地塞米松难治性骨髓瘤有效

• 发表时间: 2013
• 作者: Hiroki Kato;Yasuhi Onishi;Keiichi Ohashi;Aiko Kondou;Shin Hasegawa;Youko Okitsu;Yuuna Katsuoka;Noriko Fukuhara;Tohru Fujiwara;Junichi Kameoka;Kenichi Ishizawa;Masanori Takagawa;Hideo Harigae
• 通讯作者: Hideo Harigae

Amelioration of pulmonary artery hypertension after cord blood transplantation in an CAEBV patient

CAEBV 患者脐带血移植后肺动脉高压的改善

• 发表时间: 2013
• 作者: Yasushi Onishi;Koichiro Sugimura;Yoko Okitsu;Yuna Katsuoka;Noriko Fukuhara;Tohru Fujiwara;Junichi Kameoka;Kenichi Ishizawa;Heideo Harigae
• 通讯作者: Heideo Harigae

melioration of pulmonary artery hypertension after cord blood transplantation in an CAEBV patient

CAEBV 患者脐带血移植后肺动脉高压的改善

• 发表时间: 2013
• 作者: Yasushi Onishi;Koichiro Sugimura;Yoko Okitsu;Yuna Katsuoka;Noriko Fukuhara;Tohru Fujiwara;Junichi Kameoka;Kenichi Ishizawa;Heideo Harigae
• 通讯作者: Heideo Harigae

成人再生不良性貧血に対する同種造血幹細胞移植におけるフルダラビン+シクロホスファミドを含む前処置の検討

氟达拉滨+环磷酰胺预处理在异基因造血干细胞移植治疗成人再生障碍性贫血中的探讨

• 发表时间: 2013
• 作者: 大西康;甲斐龍幸;松本勇人;原崎頼子;佐々木治;木村秀夫;小川一英;張替秀郎
• 通讯作者: 張替秀郎

Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia

• DOI: 10.3324/haematol.2012.076042
• 发表时间: 2013-05-01
• 期刊: HAEMATOLOGICA
• 影响因子: 10.1
• 作者: Atsuta, Yoshiko;Kanda, Junya;Kanda, Yoshinobu
• 通讯作者: Kanda, Yoshinobu