title: DC-STAMP knock-down deregulates cytokine production and T-cell stimulatory capacity of LPS-matured dendritic cells.
abstract: BACKGROUND
  Dendritic cells (DCs) are the highly specialized antigen presenting cells of the immune system that play a key role in regulating immune responses. DCs can efficiently initiate immune responses or induce tolerance. Due to this dual function, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. Characterization of DC-specific genes, leading to better understanding of DC immunobiology, will help to guide their use in clinical settings. We previously identified DC-STAMP, a multi-membrane spanning protein preferentially expressed by DCs. DC-STAMP resides in the endoplasmic reticulum (ER) of immature DCs and translocates towards the Golgi compartment upon maturation. In this study we knocked down DC-STAMP in mouse bone marrow-derived DCs (mBMDCs) to determine its function.
  
  
  RESULTS
  We demonstrate that DC-STAMP knock-down mBMDCs secrete less IL-6, IL-12, TNF-α and IL-10 while IL-1 production is enhanced. Moreover, LPS-matured DC-STAMP knock-down mBMDCs show impaired T cell activation potential and induction of Th1 responses in an alloreaction.
  
  
  CONCLUSIONS
  We show that DC-STAMP plays an important role in cytokine production by mBMDCs following LPS exposure. Our results reveal a novel function of DC-STAMP in regulating DC-initiated immune responses.
authors: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Anna
authors: A
authors: Sanecka
authors: Marleen
authors: M
authors: Ansems
authors: Amy C
authors: AC
authors: Prosser
authors: Katharina
authors: K
authors: Danielski
authors: Kathrin
authors: K
authors: Warner
authors: Martijn H
authors: MH
authors: den Brok
authors: Bastiaan J H
authors: BJ
authors: Jansen
authors: Dagmar
authors: D
authors: Eleveld-Trancikova
authors: Gosse J
authors: GJ
authors: Adema
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D055785:Gene Knockdown Techniques; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; C499636:DC-STAMP protein, mouse; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering