SLAM/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte-derived dendritic cells.
Signaling lymphocyte activation molecule (SLAM, CD150, or SLAMF1) is a self-ligand receptor on the surface of activated T- and B-lymphocytes, macrophages, and dendritic cells (DCs). Here we examine the effect of SLAM/SLAM interactions on CD40L-induced CD40 signaling pathways in human DCs. CD40L-expressing L929 cells induced DCs to produce interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and IL-12, which was strongly inhibited by coexpression of SLAM on the surface of the L929 cells. Similarly, transfection of DCs with SLAM strongly reduced CD40L-induced IL-12 production. Furthermore, the negative effect of SLAM/SLAM interactions on CD40L-induced DC activation was also detected in the presence of lipopolysaccharide (LPS). LPS-induced IL-12 secretion, however, was not inhibited by SLAM engagement. CD40L-activated DCs affected by exposure to SLAM/SLAM engagement were impaired in their ability to induce differentiation of naive T lymphocytes into interferon-gamma (IFN-gamma)-producing T-helper 1 (Th1) effector cells. These inhibitory effects were not the result of a general unresponsiveness of DCs to CD40L, as SLAM/SLAM interactions did not prevent CD40L-induced up-regulation of CD83, CD86, or human leukocyte antigen (HLA)-DQ on the surface of DCs. Taken together, the results indicate that SLAM/SLAM interactions inhibit CD40-induced signal transduction in monocyte-derived dendritic cells, an effect that was not detectable in earlier studies using anti-SLAM monoclonal antibodies.
Réthi
Bence
B
Institute of Immunology, University of Debrecen Medical and Health Science Center, 98 Nagyerdei krt, H-4012 Debrecen, Hungary.
Gogolák
Péter
P
Szatmari
Istvan
I
Veres
Agota
A
Erdôs
Erika
E
Nagy
Laszlo
L
Rajnavölgyi
Eva
E
Terhorst
Cox
C
Lányi
Arpád
A
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D018189:Immunomagnetic Separation; D007249:Inflammation / Q000276:immunology; D007739:L Cells; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014162:Transfection
D015703:Antigens, CD; D019013:CD40 Antigens; D016207:Cytokines; D017931:DNA Primers; D006023:Glycoproteins; D007136:Immunoglobulins; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C000604062:Slamf1 protein, mouse; D023201:CD40 Ligand; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1