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Int. J. Mol. Sci. 2016, 17(8), 1288;

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

Department of Haematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
Second Clinical Medical College, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
Author to whom correspondence should be addressed.
Academic Editors: Anthony Lemarié and Vera Sau-Fong Chan
Received: 6 April 2016 / Revised: 12 July 2016 / Accepted: 3 August 2016 / Published: 11 August 2016
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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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. View Full-Text

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Tu, S.; Zhong, D.; Xie, W.; Huang, W.; Jiang, Y.; Li, Y. Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases. Int. J. Mol. Sci. 2016, 17, 1288.

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