The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation
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 alloreactive donor T cell...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00337/full |
| _version_ | 1811339974258196480 |
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| author | Simon eHeidegger Marcel R. M. van den Brink Tobias eHaas Hendrik ePoeck Hendrik ePoeck |
| author_facet | Simon eHeidegger Marcel R. M. van den Brink Tobias eHaas Hendrik ePoeck Hendrik ePoeck |
| author_sort | Simon eHeidegger |
| collection | DOAJ |
| description | 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 alloreactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs) such as toll-like (TLR) and nod-like receptors (NLR) are critically involved in the pathogenesis of acute GVHD. A now widely accepted model postulates that intensive chemotherapy and / or total-body irradiation during pre-transplant conditioning result 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 (APCs) to trigger the production of pro-inflammatory cytokines (‘cytokine storm’) that modulate T cell alloreactivity 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 which govern GVHD vs 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. |
| first_indexed | 2024-04-13T18:34:33Z |
| format | Article |
| id | doaj.art-b7f98154f10f46f8847c8384505e3e8d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T18:34:33Z |
| publishDate | 2014-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b7f98154f10f46f8847c8384505e3e8d2022-12-22T02:34:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-07-01510.3389/fimmu.2014.0033796047The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantationSimon eHeidegger0Marcel R. M. van den Brink1Tobias eHaas2Hendrik ePoeck3Hendrik ePoeck4Technische Universität MünchenMemorial Sloan-Kettering Cancer CenterTechnische Universität MünchenTechnische Universität MünchenMemorial Sloan-Kettering Cancer CenterAllogeneic 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 alloreactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs) such as toll-like (TLR) and nod-like receptors (NLR) are critically involved in the pathogenesis of acute GVHD. A now widely accepted model postulates that intensive chemotherapy and / or total-body irradiation during pre-transplant conditioning result 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 (APCs) to trigger the production of pro-inflammatory cytokines (‘cytokine storm’) that modulate T cell alloreactivity 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 which govern GVHD vs 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00337/fullmicrobiotaPattern-recognition receptorsgraft-versus-host diseaseallogenic hematopoietic stem cell transplantationinflammsomedanger molecules |
| spellingShingle | Simon eHeidegger Marcel R. M. van den Brink Tobias eHaas Hendrik ePoeck Hendrik ePoeck The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation Frontiers in Immunology microbiota Pattern-recognition receptors graft-versus-host disease allogenic hematopoietic stem cell transplantation inflammsome danger molecules |
| title | The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation |
| title_full | The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation |
| title_fullStr | The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation |
| title_full_unstemmed | The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation |
| title_short | The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation |
| title_sort | role of pattern recognition receptors in graft versus host disease and graft versus leukemia after allogeneic stem cell transplantation |
| topic | microbiota Pattern-recognition receptors graft-versus-host disease allogenic hematopoietic stem cell transplantation inflammsome danger molecules |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00337/full |
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