title: Characterization of species-specific genes regulated by E2-2 in human plasmacytoid dendritic cells.
abstract: Dendritic cells (DCs) are sentinels of the immune system and comprise two distinct subsets: conventional DCs (cDCs) and plasmacytoid DCs (pDCs). Human pDCs are distinguished from mouse pDCs phenotypically and functionally. Basic helix-loop-helix protein E2-2 is defined as an essential transcription factor for mouse pDC development, cell fate maintenance and gene programe. It is unknown whether E2-2 regulation contributes to this species-specific difference. Here we investigated the function of E2-2 in human pDCs and screened human-specific genes regulated by E2-2. Reduced E2-2 expression in human pDC cell line GEN2.2 resulted in diminished IFN-α production in response to CpG but elevated antigen presentation capacity. Gene expression profiling showed that E2-2 silence down-regulated pDC signature genes but up-regulated cDC signature genes. Thirty human-specific genes regulated by E2-2 knockdown were identified. Among these genes, we confirmed that expression of Siglec-6 was inhibited by E2-2. Further more, Siglec-6 was expressed at a higher level on a human pDC subset with drastically lower expression of E2-2. Collectively, these results highlight that E2-2 modulates pDC function in a species-specific manner, which may provide insights for pDC development and functions.
authors.affiliation: Key Laboratory of Immunity and Infection, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Menglan
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Immunity and Infection, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xuyuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Immunity and Infection, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Key Laboratory of Immunity and Infection, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Peishuang
authors.initials: P
authors.lastname: Du
authors.affiliation: Department of Research and Development, EFS Rh ône-Alpes Grenoble, La Tronche, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Plumas
authors.affiliation: Department of Research and Development, EFS Rh ône-Alpes Grenoble, La Tronche, France.
authors.forename: Laurance
authors.initials: L
authors.lastname: Chaperot
authors.affiliation: 1] Key Laboratory of Immunity and Infection, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing, China [2] Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
authors.affiliation: Key Laboratory of Immunity and Infection, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D034741:RNA, Small Interfering; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein