title: Pathogenesis of graft-versus-host disease: innate immunity amplifying acute alloimmune responses.
abstract: In addition to reduced-intensity conditioning, which has expanded the eligibility for hematopoietic cell transplantation (HCT) to older patients, increased availability of alternative donors, including HLA-mismatched unrelated donors, has increased access to allogeneic HCT for more patients. However, acute graft-versus-host disease (GVHD) remains a lethal complication, even in HLA-matched donor-recipient pairs. The pathophysiology of GVHD depends on aspects of adaptive immunity and interactions between donor T-cells and host dendritic cells (DCs). Recent work has revealed that the role of other immune cells and endothelial cells and components of the innate immune response are also important. Tissue damage caused by the conditioning regimen leads to the release of exogenous and endogenous "danger signals". Exogenous danger signals called pathogen-associated molecular patterns and endogenous noninfectious molecules known as damage-associated molecular patterns (DAMPs) are responsible for initiating or amplifying acute GVHD by enhancing DC maturation and alloreactive T-cell responses. A significant association of innate immune receptor polymorphisms with outcomes, including GVHD severity, was observed in patients receiving allogeneic HCT. Understanding of the role of innate immunity in acute GVHD might offer new therapeutic approaches.
authors: Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama, Okayama, 700-8558, Japan, yosmaeda@md.okayama-u.ac.jp.
authors: Yoshinobu
authors: Y
authors: Maeda
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000502:physiology; D064591:Allografts; D003713:Dendritic Cells / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D024243:HMGB1 Protein / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006497:Heparan Sulfate / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000502:physiology; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D058990:Molecular Targeted Therapy; D053472:Nod Signaling Adaptor Proteins / Q000502:physiology; D011110:Polymorphism, Genetic; D009418:S100 Proteins / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D019172:Transplantation Conditioning / Q000009:adverse effects
chemical_list: D000255:Adenosine Triphosphate; D024243:HMGB1 Protein; D006360:Heat-Shock Proteins; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D007519:Isoantigens; D053472:Nod Signaling Adaptor Proteins; D009418:S100 Proteins; D051193:Toll-Like Receptors; C585491:HMGB1 protein, human
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