Pathogenesis of graft-versus-host disease: Innate immunity amplifying acute alloimmune responses

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21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)293-299
Number of pages7
JournalInternational Journal of Hematology
Volume98
Issue number3
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Graft vs Host Disease
Innate Immunity
Cell Transplantation
Tissue Donors
Dendritic Cells
T-Lymphocytes
Unrelated Donors
Adaptive Immunity
Cellular Structures
Endothelial Cells

Keywords

  • DAMPs
  • Danger signals
  • GVHD
  • Innate immunity
  • PAMPs

ASJC Scopus subject areas

  • Hematology

Cite this

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