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学科主题: 口腔医学
题名:
FOXO1 Regulates Dendritic Cell Activity through ICAM-1 and CCR7
作者: Dong, Guangyu1,2; Wang, Yu1; Xiao, Wenmei1,3; Pujado, Sandra Pacios1; Xu, Fanxing1,4; Tian, Chen1; Xiao, E.1,5; Choi, Yongwon6; Graves, Dana T.1
刊名: JOURNAL OF IMMUNOLOGY
发表日期: 2015-04-15
DOI: 10.4049/jimmunol.1401754
卷: 194, 期:8, 页:3745-+
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology
研究领域[WOS]: Immunology
关键词[WOS]: CD4(+) T-CELLS ; IN-VIVO ; B-CELLS ; RESPONSES ; MIGRATION ; ANTIGEN ; MECHANISMS ; EXPRESSION ; INNATE ; STIMULATION
英文摘要:

The transcription factor FOXO1 regulates cell function and is expressed in dendritic cells (DCs). We investigated the role of FOXO1 in activating DCs to stimulate a lymphocyte response to bacteria. We show that bacteria induce FOXO1 nuclear localization through the MAPK pathway and demonstrate that FOXO1 is needed for DC activation of lymphocytes in vivo. This occurs through FOXO1 regulation of DC phagocytosis, chemotaxis, and DC-lymphocyte binding. FOXO1 induces DC activity by regulating ICAM-1 and CCR7. FOXO1 binds to the CCR7 and ICAM-1 promoters, stimulates CCR7 and ICAM-1 transcriptional activity, and regulates their expression. This is functionally important because transfection of DCs from FOXO1-deleted CD11c. Cre(+)FOXO1(L/L) mice with an ICAM-1-expressing plasmid rescues the negative effect of FOXO1 deletion on DC bacterial phagocytosis and chemotaxis. Rescue with both CCR7 and ICAM-1 reverses impaired DC homing to lymph nodes in vivo when FOXO1 is deleted. Moreover, Ab production following injection of bacteria is significantly reduced with lineage-specific FOXO1 ablation. Thus, FOXO1 coordinates upregulation of DC activity through key downstream target genes that are needed for DCs to stimulate T and B lymphocytes and generate an Ab defense to bacteria.

语种: 英语
所属项目编号: DE-019108 ; DE-021921
项目资助者: National Institutes of Health
WOS记录号: WOS:000353247000023
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56284
Appears in Collections:北京大学口腔医学院_牙周科_期刊论文

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作者单位: 1.Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA
2.Jilin Univ, Sch Stomatol, Dept Implantol, Changchun 130021, Peoples R China
3.Peking Univ, Sch & Hosp Stomatol, Dept Periodontol, Beijing 100081, Peoples R China
4.Dalian Univ Technol, Sch Life Sci & Biotechnol, Dalian 116024, Peoples R China
5.Peking Univ, Dept Oral & Maxillofacial Surg, Sch & Hosp Stomatol, Beijing 100081, Peoples R China
6.Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Recommended Citation:
Dong, Guangyu,Wang, Yu,Xiao, Wenmei,et al. FOXO1 Regulates Dendritic Cell Activity through ICAM-1 and CCR7[J]. JOURNAL OF IMMUNOLOGY,2015,194(8):3745-+.
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