title: Transcription factor E2F1 suppresses dendritic cell maturation.
abstract: Transcription factor E2F1 has been largely studied as a promoter of S-phase transition in the cell cycle and as a regulator of apoptosis. Recently, E2F1 has been shown to regulate a wide range of genes in response to inflammatory stimulation of macrophages and to contribute to T cell activation in response to pathogens, implicating an extensive immunological role for E2F1. Dendritic cells (DCs) play critical roles as professional APCs in the development of immune responses. However, it is unclear whether E2F1 has any effect on DC phenotype or function. In this paper, we report that E2F1 acts as a suppressor of DC maturation. The level of E2F1 expression was transiently downregulated in the course of LPS-induced maturation of both human monocyte-derived DCs and a mouse DC cell line, DC2.4. Knockdown of E2F1 by small interfering RNA in DC2.4 cells resulted in both phenotypic and functional maturation, even without LPS treatment. Conversely, ectopic overexpression of E2F1 suppressed LPS-induced maturation of DC2.4 cells. Furthermore, knockdown of E2F1 caused the activation of several major signaling pathways known to be activated in the course of DC maturation, including Erk1/2, NF-kappaB, and PI3K/Akt, suggesting that E2F1 may be involved in regulating multiple signaling pathways in DCs. Finally, the alteration of phenotypic maturation by E2F1 was confirmed with bone marrow-derived DCs from E2F1 knockout mice. Overall, our data demonstrate for the first time that E2F1 is a critical regulator of DC maturation.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Ma
authors.forename: Zijia
authors.initials: Z
authors.lastname: Ren
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: De
authors.initials: D
authors.lastname: Yang
authors.forename: Weihua
authors.initials: W
authors.lastname: Xiao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D050687:E2F1 Transcription Factor