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

Frontiers in Immunology

Marcel R. M. van den Brink¹  Hendrik ePoeck¹  Simon eHeidegger²  Tobias eHaas² 

[1] Memorial Sloan-Kettering Cancer Center;Technische Universität München;

关键词: microbiota;    Pattern-recognition receptors;    graft-versus-host disease;    allogenic hematopoietic stem cell transplantation;    inflammsome;    danger molecules;   

DOI  :  10.3389/fimmu.2014.00337

来源: DOAJ

【 摘 要 】

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 mayultimately 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.

【 授权许可】

Unknown