Inflammatory Regulation by TLR3 in Acute Hepatitis
Xiaoyan Xiao,Peng Zhao,Daniel Rodriguez-Pinto,Dake Qi,Octavian Henegariu,Lena Alexopoulou,Richard A. Flavell,F. Susan Wong,Li Wen +8 more
TLDR
The data suggest thatTLR3 signaling is necessary for Con A-induced liver damage in vivo and that TLR3 regulates inflammation and the adaptive T cell immune response in the absence of viral infection.Abstract:
TLR3 is known to respond to dsRNA from viruses, apoptotic cells, and/or necrotic cells. Dying cells are a rich source of ligands that can activate TLRs, such as TLR3. TLR3 expressed in the liver is likely to be a mediator of innate activation and inflammation in the liver. The importance of this function of TLR3 during acute hepatitis has not previously been fully explored. We used the mouse model of Con A-induced hepatitis and observed a novel role for TLR3 in hepatocyte damage in the absence of an exogenous viral stimulus. Interestingly, TLR3 expression in liver mononuclear cells and sinus endothelial cells was up-regulated after Con A injection and TLR3−/− mice were protected from Con A-induced hepatitis. Moreover, splenocytes from TLR3−/− mice proliferated less to Con A stimulation in the presence of RNA derived from damaged liver tissue compared with wild-type (WT) mice. To determine the relative contribution of TLR3 expression by hematopoietic cells or nonhematopoietic to liver damage during Con A-induced hepatitis, we generated bone marrow chimeric mice. TLR3−/− mice engrafted with WT hematopoietic cells were protected in a similar manner to WT mice reconstituted with TLR3−/− bone marrow, indicating that TLR3 signaling in both nonhematopoietic and hematopoietic cells plays an important role in mediating liver damage. In summary, our data suggest that TLR3 signaling is necessary for Con A-induced liver damage in vivo and that TLR3 regulates inflammation and the adaptive T cell immune response in the absence of viral infection.read more
Citations
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IL-33/ST2 axis in inflammation and immunopathology
Marija Milovanovic,Vladislav Volarevic,Gordana Radosavljevic,Ivan Jovanovic,Nada Pejnovic,Nebojsa Arsenijevic,Miodrag L. Lukic +6 more
TL;DR: It is observed that IL-33 has attenuated anti-inflammatory effects in T cell-mediated responses and that both IL- 33 and ST2 could be further explored as potential therapeutic targets in treatment of immune-mediated diseases.
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Protective role of IL-33/ST2 axis in Con A-induced hepatitis.
Vladislav Volarevic,Marina Mitrovic,Marija Milovanovic,Ivanka Zelen,Ivana Nikolic,Slobodanka Mitrovic,Nada Pejnovic,Nebojsa Arsenijevic,Miodrag L. Lukic +8 more
TL;DR: It is concluded that Interleukin 33/ST2 axis downregulated Concanavalin A-induced liver injury and should be evaluated as potential target in fulminant hepatitis in humans.
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Melatonin protects liver against ischemia and reperfusion injury through inhibition of toll‐like receptor signaling pathway
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Role of Toll-like receptors in immune activation and tolerance in the liver
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TL;DR: The current understanding of TLR signaling and subsequent immune activation and tolerance by the innate immune system in the liver is reviewed, and the dual role of disease-specific TLRs as activators and regulators is clarified.
References
More filters
Journal ArticleDOI
Pathogen Recognition and Innate Immunity
TL;DR: New insights into innate immunity are changing the way the way the authors think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.
Journal ArticleDOI
Toll-like receptor signalling
Shizuo Akira,Kiyoshi Takeda +1 more
TL;DR: Rapid progress that has recently improved the understanding of the molecular mechanisms that mediate TLR signalling is reviewed.
Journal ArticleDOI
Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.
TL;DR: It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).
Journal ArticleDOI
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
TL;DR: The cloning and characterization of a human homologue of the Drosophila toll protein (Toll) is reported, which has been shown to induce the innate immune response in adult Dosophila.
Journal ArticleDOI
Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE.
Jane Tian,Ana M. Avalos,Su-Yau Mao,Bo Chen,Kannaki Senthil,Herren Wu,Peggy Parroche,Stacey Drabic,Douglas T. Golenbock,Cherilyn M. Sirois,Jing Hua,Ling-Ling An,Laurent P. Audoly,Greg La Rosa,Angelika Bierhaus,Peter Naworth,Ann Marshak-Rothstein,Mary K. Crow,Katherine A. Fitzgerald,Eicke Latz,Peter A. Kiener,Anthony J. Coyle +21 more
TL;DR: HMGB1, a nuclear DNA-binding protein released from necrotic cells, was an essential component of DNA-containing immune complexes that stimulated cytokine production through a TLR9–MyD88 pathway involving the multivalent receptor RAGE.
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