FOXO1 regulates dendritic cell activity through ICAM-1 and CCR7

The Journal of Immunology : Official Journal of the American Association of Immunologists
Guangyu DongDana T Graves

Abstract

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...Continue Reading

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Citations

Nov 8, 2016·The Journal of Clinical Investigation·Kiwon ParkCatherine C Hedrick
Nov 29, 2016·Transplantation·Liang WeiSheri M Krams
Jul 18, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takuya YashiroChiharu Nishiyama
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Apr 17, 2021·Journal of Immunology Research·Liang RenChengcheng Liu
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