The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation Journal Article

   

Authors:	Heidegger, S.; van den Brink, M. R. M.; Haas, T.; Poeck, H.
Article Title:	The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation
Abstract:	Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential for certain aggressive hematopoietic malignancies. Its success is limited by acute graft-versus-host disease (GVHD), a life-threatening complication that occurs when allo-reactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs) such as toll-like receptors (TLR) and nod-like receptors (NLR) are critically involved in the pathogenesis of acute GVHD. Currently, a widely accepted model postulates that intensive chemotherapy and/or total-body irradiation during pre-transplant conditioning results in tissue damage and a loss of epithelial barrier function. Subsequent translocation of bacterial components as well as release of endogenous danger molecules stimulate PRRs of host antigen-presenting cells to trigger the production of pro-inflammatory cytokines (cytokine storm) that modulate T cell allo-reactivity against host tissues, but eventually also the beneficial graft-versus-leukemia (GVL) effect. Given the limitations of existing immunosuppressive therapies, a better understanding of the molecular mechanisms that govern GVHD versus GVL is urgently needed. This may ultimately allow to design modulators, which protect from GvHD but preserve donor T-cell attack on hematologic malignancies. Here, we will briefly summarize current knowledge about the role of innate immunity in the pathogenesis of GVHD and GVL following allo-HSCT. © 2014 Heidegger, van den Brink, Haas and Poeck.
Keywords:	graft-versus-host disease; microbiota; pattern-recognition receptors; allogenic hematopoietic stem cell transplantation; danger molecules; inflammsome
Journal Title:	Frontiers in Immunology
Volume:	5
ISSN:	1664-3224
Publisher:	Frontiers Media S.A.
Date Published:	2014-07-18
Start Page:	337
Language:	English
DOI:	10.3389/fimmu.2014.00337
PROVIDER:	scopus
PMCID:	PMC4102927
PUBMED:	25101080
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84905661901&partnerID=40&md5=09b5db83b956cd62f4091d81c1462c96
Notes:	Export Date: 2 September 2014 -- Source: Scopus

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