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The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA

Toll-like Receptor 9 (TLR9) is an innate immune receptor recognizing microbial DNA. TLR9 is also activated by self-derived DNA, such as mitochondrial DNA, in a variety of inflammatory diseases. We show here that TLR9 activation in vivo is controlled by an anti-TLR9 monoclonal Ab (mAb). A newly estab...

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Autores principales: Murakami, Yusuke, Fukui, Ryutaro, Motoi, Yuji, Shibata, Takuma, Saitoh, Shin-Ichiroh, Sato, Ryota, Miyake, Kensuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339793/
https://www.ncbi.nlm.nih.gov/pubmed/28266597
http://dx.doi.org/10.1038/srep44042
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author Murakami, Yusuke
Fukui, Ryutaro
Motoi, Yuji
Shibata, Takuma
Saitoh, Shin-Ichiroh
Sato, Ryota
Miyake, Kensuke
author_facet Murakami, Yusuke
Fukui, Ryutaro
Motoi, Yuji
Shibata, Takuma
Saitoh, Shin-Ichiroh
Sato, Ryota
Miyake, Kensuke
author_sort Murakami, Yusuke
collection PubMed
description Toll-like Receptor 9 (TLR9) is an innate immune receptor recognizing microbial DNA. TLR9 is also activated by self-derived DNA, such as mitochondrial DNA, in a variety of inflammatory diseases. We show here that TLR9 activation in vivo is controlled by an anti-TLR9 monoclonal Ab (mAb). A newly established mAb, named NaR9, clearly detects endogenous TLR9 expressed in primary immune cells. The mAb inhibited TLR9-dependent cytokine production in vitro by bone marrow-derived macrophages and conventional dendritic cells. Furthermore, NaR9 treatment rescued mice from fulminant hepatitis caused by administering the TLR9 ligand CpGB and D-(+)-galactosamine. The production of proinflammatory cytokines induced by CpGB and D-(+)-galactosamine was significantly impaired by the mAb. These results suggest that a mAb is a promising tool for therapeutic intervention in TLR9-dependent inflammatory diseases.
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spelling pubmed-53397932017-03-10 The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA Murakami, Yusuke Fukui, Ryutaro Motoi, Yuji Shibata, Takuma Saitoh, Shin-Ichiroh Sato, Ryota Miyake, Kensuke Sci Rep Article Toll-like Receptor 9 (TLR9) is an innate immune receptor recognizing microbial DNA. TLR9 is also activated by self-derived DNA, such as mitochondrial DNA, in a variety of inflammatory diseases. We show here that TLR9 activation in vivo is controlled by an anti-TLR9 monoclonal Ab (mAb). A newly established mAb, named NaR9, clearly detects endogenous TLR9 expressed in primary immune cells. The mAb inhibited TLR9-dependent cytokine production in vitro by bone marrow-derived macrophages and conventional dendritic cells. Furthermore, NaR9 treatment rescued mice from fulminant hepatitis caused by administering the TLR9 ligand CpGB and D-(+)-galactosamine. The production of proinflammatory cytokines induced by CpGB and D-(+)-galactosamine was significantly impaired by the mAb. These results suggest that a mAb is a promising tool for therapeutic intervention in TLR9-dependent inflammatory diseases. Nature Publishing Group 2017-03-07 /pmc/articles/PMC5339793/ /pubmed/28266597 http://dx.doi.org/10.1038/srep44042 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Murakami, Yusuke
Fukui, Ryutaro
Motoi, Yuji
Shibata, Takuma
Saitoh, Shin-Ichiroh
Sato, Ryota
Miyake, Kensuke
The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA
title The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA
title_full The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA
title_fullStr The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA
title_full_unstemmed The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA
title_short The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA
title_sort protective effect of the anti-toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory dna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339793/
https://www.ncbi.nlm.nih.gov/pubmed/28266597
http://dx.doi.org/10.1038/srep44042
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