TLR3 signaling is downregulated by a MAVS isoform in epithelial cells.
Innate immune responses to dsRNA result in signaling through the TLR3 pathway and/or the RIG-I/MDA-5/MAVS pathway which can activate type I IFN, proinflammatory cytokines and apoptosis. It is not clear whether MAVS could play a role in TLR3-dependent responses to extracellular dsRNA. Using a model of epithelial cells that express a functional TLR3 signaling pathway, we found that TLR3-dependent responses to extracellular dsRNA are negatively regulated by MAVS, precisely "miniMAVS", a recently described 50kDa isoform of MAVS. This regulation of TLR3 by a MAVS isoform constitutes an endogenous regulatory mechanism in epithelial cells that could help prevent a potentially damaging excessive inflammatory response.
Laboratory of Mucosal Immunology, University of California San Diego, La Jolla, CA 92093, United States; Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States. Electronic address: olakhdari@ucsd.edu.
Omar
O
Lakhdari
Laboratory of Mucosal Immunology, University of California San Diego, La Jolla, CA 92093, United States; Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States.
Christopher S
CS
McAllister
Laboratory of Mucosal Immunology, University of California San Diego, La Jolla, CA 92093, United States; Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States.
Michael
M
Wang
Laboratory of Mucosal Immunology, University of California San Diego, La Jolla, CA 92093, United States; Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States.
Ivelina
I
Minev
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, United States.
Lawrence S
LS
Prince
Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States.
Lars
L
Eckmann
Laboratory of Mucosal Immunology, University of California San Diego, La Jolla, CA 92093, United States; Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, United States.
Martin F
MF
Kagnoff
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D004847:Epithelial Cells / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C494232:IRF3 protein, human; D018836:Inflammation Mediators; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D016328:NF-kappa B; D020033:Protein Isoforms; D034741:RNA, Small Interfering; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C
Epithelial cells; HCT116; Interferon beta; Isoform; MAVS; Regulation; TLR3; miniMAVS