Endogenous control of immunity against infection: tenascin-C regulates TLR4-mediated inflammation via microRNA-155.
Endogenous molecules generated upon pathogen invasion or tissue damage serve as danger signals that activate host defense; however, their precise immunological role remains unclear. Tenascin-C is an extracellular matrix glycoprotein that is specifically induced upon injury and infection. Here, we show that its expression is required to generate an effective immune response to bacterial lipopolysaccharide (LPS) during experimental sepsis in vivo. Tenascin-C enables macrophage translation of proinflammatory cytokines upon LPS activation of toll-like receptor 4 (TLR4) and suppresses the synthesis of anti-inflammatory cytokines. It mediates posttranscriptional control of a specific subset of inflammatory mediators via induction of the microRNA miR-155. Thus, tenascin-C plays a key role in regulating the inflammatory axis during pathogenic activation of TLR signaling.
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, 65 Aspenlea Road, London W6 8LH, UK.
Anna M
AM
Piccinini
Kim S
KS
Midwood
D000818:Animals; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000378:metabolism; D007239:Infections / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D018805:Sepsis / Q000209:etiology / Q000276:immunology; D015398:Signal Transduction; D019063:Tenascin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D019063:Tenascin; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha