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Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases

Graft-versus-host disease (GVHD) and infection are major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the leading causes of morbidity and mortality in HSCT patients. Recent work has demonstrated that the two complications are interdependent. GVHD occurs when...

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Autores principales: Tu, Sanfang, Zhong, Danli, Xie, Weixin, Huang, Wenfa, Jiang, Yangyang, Li, Yuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000685/
https://www.ncbi.nlm.nih.gov/pubmed/27529218
http://dx.doi.org/10.3390/ijms17081288
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author Tu, Sanfang
Zhong, Danli
Xie, Weixin
Huang, Wenfa
Jiang, Yangyang
Li, Yuhua
author_facet Tu, Sanfang
Zhong, Danli
Xie, Weixin
Huang, Wenfa
Jiang, Yangyang
Li, Yuhua
author_sort Tu, Sanfang
collection PubMed
description Graft-versus-host disease (GVHD) and infection are major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the leading causes of morbidity and mortality in HSCT patients. Recent work has demonstrated that the two complications are interdependent. GVHD occurs when allo-reactive donor T lymphocytes are activated by major histocompatibility antigens or minor histocompatibility antigens on host antigen-presenting cells (APCs), with the eventual attack of recipient tissues or organs. Activation of APCs is important for the priming of GVHD and is mediated by innate immune signaling pathways. Current evidence indicates that intestinal microbes and innate pattern-recognition receptors (PRRs) on host APCs, including both Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs), are involved in the pathogenesis of GVHD. Patients undergoing chemotherapy and/or total body irradiation before allo-HSCT are susceptible to aggravated gastrointestinal epithelial cell damage and the subsequent translocation of bacterial components, followed by the release of endogenous dangerous molecules, termed pathogen-associated molecular patterns (PAMPs), which then activate the PRRs on host APCs to trigger local or systemic inflammatory responses that modulate T cell allo-reactivity against host tissues, which is equivalent to GVHD. In other words, infection can, to some extent, accelerate the progression of GVHD. Therefore, the intestinal flora’s PAMPs can interact with TLRs to activate and mature APCs, subsequently activate donor T cells with the release of pro-inflammatory cytokines, and eventually, induce GVHD. In the present article, we summarize the current perspectives on the understanding of different TLR signaling pathways and their involvement in the occurrence of GVHD.
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spelling pubmed-50006852016-09-01 Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases Tu, Sanfang Zhong, Danli Xie, Weixin Huang, Wenfa Jiang, Yangyang Li, Yuhua Int J Mol Sci Review Graft-versus-host disease (GVHD) and infection are major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the leading causes of morbidity and mortality in HSCT patients. Recent work has demonstrated that the two complications are interdependent. GVHD occurs when allo-reactive donor T lymphocytes are activated by major histocompatibility antigens or minor histocompatibility antigens on host antigen-presenting cells (APCs), with the eventual attack of recipient tissues or organs. Activation of APCs is important for the priming of GVHD and is mediated by innate immune signaling pathways. Current evidence indicates that intestinal microbes and innate pattern-recognition receptors (PRRs) on host APCs, including both Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs), are involved in the pathogenesis of GVHD. Patients undergoing chemotherapy and/or total body irradiation before allo-HSCT are susceptible to aggravated gastrointestinal epithelial cell damage and the subsequent translocation of bacterial components, followed by the release of endogenous dangerous molecules, termed pathogen-associated molecular patterns (PAMPs), which then activate the PRRs on host APCs to trigger local or systemic inflammatory responses that modulate T cell allo-reactivity against host tissues, which is equivalent to GVHD. In other words, infection can, to some extent, accelerate the progression of GVHD. Therefore, the intestinal flora’s PAMPs can interact with TLRs to activate and mature APCs, subsequently activate donor T cells with the release of pro-inflammatory cytokines, and eventually, induce GVHD. In the present article, we summarize the current perspectives on the understanding of different TLR signaling pathways and their involvement in the occurrence of GVHD. MDPI 2016-08-11 /pmc/articles/PMC5000685/ /pubmed/27529218 http://dx.doi.org/10.3390/ijms17081288 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tu, Sanfang
Zhong, Danli
Xie, Weixin
Huang, Wenfa
Jiang, Yangyang
Li, Yuhua
Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases
title Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases
title_full Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases
title_fullStr Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases
title_full_unstemmed Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases
title_short Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases
title_sort role of toll-like receptor signaling in the pathogenesis of graft-versus-host diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000685/
https://www.ncbi.nlm.nih.gov/pubmed/27529218
http://dx.doi.org/10.3390/ijms17081288
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