PU.1 regulates the tissue-specific expression of dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin.
Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a cell surface C-type lectin expressed on myeloid dendritic cells and certain tissue macrophages, which mediates antigen capture for processing and presentation and participates in intercellular interactions with naive T lymphocytes or endothelial cells. In their strategy to evade immunosurveillance, numerous pathogenic microorganisms, including human immunodeficiency virus and Mycobacterium, bind to DC-SIGN in order to gain access to dendritic cells. We present evidence that PU.1 dictates the basal and cell-specific activity of DC-SIGN gene-regulatory region through in vivo occupancy of two functional Ets elements, whose integrity is required for PU.1 responsiveness and for the cooperative actions of PU.1 and other transcription factors (Myb, RUNX) on the DC-SIGN gene proximal regulatory region. In addition, protein analysis and gene profiling experiments indicate that DC-SIGN and PU.1 are coordinately expressed upon classical and alternative macrophage activation and during dendritic cell maturation. Moreover, small interfering RNA-mediated reduction of PU.1 expression results in diminished DC-SIGN cellular levels. Altogether, these results indicate that PU.1 is involved in the myeloid-specific expression of DC-SIGN in myeloid cells, a contribution that can be framed within the role that PU.1 has on the acquisition of the antigen uptake molecular repertoire by dendritic cells and macrophages.
Domínguez-Soto
Angeles
A
Centro de Investigaciones Biológicas, CSIC, Madrid 28040, Spain.
Puig-Kröger
Amaya
A
Vega
Miguel A
MA
Corbí
Angel L
AL
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D003713:Dendritic Cells / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D019169:Jurkat Cells; D020014:K562 Cells; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008262:Macrophage Activation; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D015847:Interleukin-4; D037181:Lectins, C-Type; D011518:Proto-Oncogene Proteins; D012342:RNA, Small Nuclear; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin