Signaling lymphocytic activation molecule is expressed on CD40 ligand-activated dendritic cells and directly augments production of inflammatory cytokines.
Dendritic cells (DC) comprise a key part of the innate immune system that, upon activation, profoundly influences the nature of the adaptive T cell response. In this study, we present evidence that signaling lymphocytic activation molecule (SLAM), a molecule first identified in activated T and B cells, is strongly up-regulated in DC activated through CD40, as well as in response to inflammatory stimuli, including polyinosinic polycytidylic acid and LPS. mRNA encoding both membrane-bound and soluble secreted isoforms of SLAM was detected in CD40 ligand-activated DC, comprising two of the four known SLAM isoforms. Expression of membrane-bound SLAM protein peaked at 12 h poststimulation with CD40 ligand, gradually returning to baseline levels after 6 days. SLAM up-regulation appears to be a direct result of the induction of DC maturation, as inflammatory cytokines released during this process do not affect SLAM expression. Functionally, engagement of SLAM enhances DC production of IL-12 and IL-8, while having no effect on production of IL-10. Because SLAM is involved in the activation of T cells, the expression of SLAM on DC may provide a bidirectional signaling mechanism in which interacting DC and T cells are simultaneously and synergistically activated to mount proinflammatory Th1 responses.
Bleharski
J R
JR
Department of Medicine, Division of Dermatology, Jonsson Comprehensive Cancer Center, and Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095, USA.
Niazi
K R
KR
Sieling
P A
PA
Cheng
G
G
Modlin
R L
RL
D000328:Adult; D015703:Antigens, CD; D017209:Apoptosis / Q000235:genetics; D023201:CD40 Ligand / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology*; D011070:Poly I-C / Q000494:pharmacology; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013382:Subtraction Technique; D018417:Th1 Cells / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D023201:CD40 Ligand; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D011070:Poly I-C