TY - JOUR
T1 - DC-STAMP knock-down deregulates cytokine production and T-cell stimulatory capacity of LPS-matured dendritic cells
AU - Sanecka, Anna
AU - Ansems, Marleen
AU - Prosser, Amy C
AU - Danielski, Katharina
AU - Warner, Kathrin
AU - den Brok, Martijn H
AU - Jansen, Bastiaan J H
AU - Eleveld-Trancikova, Dagmar
AU - Adema, Gosse J
PY - 2011/10/6
Y1 - 2011/10/6
N2 - 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.
AB - 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.
KW - Animals
KW - Bone Marrow/pathology
KW - Cell Differentiation/genetics
KW - Cell Line
KW - Cytokines/genetics
KW - Dendritic Cells/immunology
KW - Female
KW - Gene Expression Regulation/genetics
KW - Gene Knockdown Techniques
KW - Humans
KW - Lipopolysaccharides/immunology
KW - Lymphocyte Activation/genetics
KW - Membrane Proteins/genetics
KW - Mice
KW - Mice, Inbred C57BL
KW - Microscopy, Confocal
KW - Nerve Tissue Proteins/genetics
KW - RNA, Small Interfering/genetics
KW - T-Lymphocytes/metabolism
UR - https://www.scopus.com/pages/publications/80053480059
U2 - 10.1186/1471-2172-12-57
DO - 10.1186/1471-2172-12-57
M3 - Article
C2 - 21978263
SN - 1471-2172
VL - 12
SP - 57
JO - BMC Immunology
JF - BMC Immunology
ER -
