title: Danger signals activating innate immunity in graft-versus-host disease.
abstract: Extensive cell death with consecutive release of danger signals can cause immune-mediated tissue destruction. The abundance of cell death is likely to determine the relevance of the danger signals as physiological mechanisms that counteract immune activation may be overruled. Such constellation is conceivable in chemo-/radiotherapy-induced tissue damage, reperfusion injury, trauma, and severe infection. Studies on graft-versus-host disease (GvHD) development have to consider the effects of chemo-/radiotherapy-related tissue damage leading to the release of exogenous and endogenous danger signals. Our previous work has demonstrated a role for adenosine-5'-triphosphate (ATP) as an endogenous danger signal in GvHD. Besides ATP, uric acid or soluble extracellular matrix components are functional danger signals that activate the NLRP3 inflammasome when released from dying cells or from extracellular matrix. In contrast to sterile inflammation, GvHD is more complex since bacterial components that leak through damaged intestinal barriers and the skin can activate pattern recognition receptors and directly contribute to GvHD pathogenesis. These exogenous danger signals transmit immune activation via toll-like receptors and NOD-like receptors of the innate immune system. This review covers both the impact of endogenous and exogenous danger signals activating innate immunity in GvHD.
authors.affiliation: Department of Hematology and Oncology, Freiburg University Medical Center, Albert-Ludwigs-University, Hugstetterstr. 55, 79106 Freiburg, Germany. robert.zeiser@uniklinik-freiburg.de
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.forename: Olaf
authors.initials: O
authors.lastname: Penack
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology / Q000378:metabolism; D000818:Animals; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000276:immunology / Q000378:metabolism
chemical_list: D051192:Receptors, Pattern Recognition; D000255:Adenosine Triphosphate