title: Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity.
abstract: Early growth response gene 2 (Egr2), which encodes a zinc finger transcription factor, is rapidly and transiently induced in various cell types independently of de novo protein synthesis. Although a role for Egr2 is well established in T-cell development, Egr2 expression and its biological function in dendritic cells (DCs) have not yet been described. Here, we demonstrate Egr2 expression during DC development, and its role in DC-mediated immune responses. Egr2 is expressed in the later stage of DC development from BM precursor cells. Even at steady state, Egr2 is highly expressed in mouse splenic DCs. Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities. Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine. DC-mediated cytotoxic T lymphocyte (CTL) activation and antitumor immunity were significantly enhanced by Egr2-KD, and impaired by Egr2 overexpression in antigen-pulsed DC vaccines. These data suggest that Egr2 acts as an intrinsic negative regulator of DC immunogenicity and can be an attractive molecular target for DC vaccine development.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea; Department of Physiology, Bangladesh Agricultural University, Mymensingh, Bangladesh.
authors.forename: Mohammad Alam
authors.initials: MA
authors.lastname: Miah
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Byeon
authors.forename: Md Selim
authors.initials: MS
authors.lastname: Ahmed
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Yoon
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D051767:Early Growth Response Protein 2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D034622:RNA Interference; D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018664:Interleukin-12
keywords: DC development; Egr2; Immunotherapy; Negative regulator; Th1 immunity