Cellular and molecular mechanisms in graft‐versus‐host disease

  title={Cellular and molecular mechanisms in graft‐versus‐host disease},
  author={Lingling Zhang and Jianhong Chu and Jianhua Yu and Wei Wei},
  journal={Journal of Leukocyte Biology},
Graft‐versus‐host disease is a complication in patients undergoing hematopoietic stem cell transplantation. Graft‐versus‐host disease includes acute graft‐versus‐host disease and chronic graft‐versus‐host disease. Host APCs (e.g., dendritic cells and macrophages), effector T cells (e.g., Th1, Th17, and abnormal Th17:regulatory T cell ratio), B cells, and NK cells are implicated in graft‐versus‐host disease physiopathology. Proinflammation cytokines (e.g., IL‐17, IL‐1β, and TNF‐α) are increased… 

Advance in Targeted Immunotherapy for Graft-Versus-Host Disease

Standard therapeutic strategies are still lacking, although considerable advances have been gained in knowing of the predisposing factors, pathology, and diagnosis of GVHD, and the identification of novel therapeutic targets and systematic research strategies may yield novel safe and effective approaches in clinic.

GVHD Pathogenesis, Prevention and Treatment: Lessons From Humanized Mouse Transplant Models

The current state of clinical GVHD research is summarized, how xenogeneic HSCT models will aid in advancing the current pipeline of novel GV HD prophylaxis therapies into the clinic is discussed and how this has allowed for the direct assessment of key factors in GVhd pathogenesis to be investigated prior to entering clinical trials.

B Lymphocytes Are the Target of Mesenchymal Stem Cells Immunoregulatory Effect in a Murine Graft-versus-Host Disease Model

B lymphocytes played an important role in the development of aGvHD, and they are targets in MSC-regulated immune response cascade in vivo, which may provide a mechanistic clue for the treatment of human clinical aGVHD.

Novel approaches for preventing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

A new understanding of the involvement of cytokines, intracellular signaling pathways, epigenetics and immunoregulatory cells in GVHD pathogenesis will lead to new standards for aGV HD prophylaxis allowing better prevention of severe aGVHD without affecting graft-versus-tumor effects.

Immunomodulating functions of human leukocyte antigen-G and its role in graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

The immunomodulatory properties of human leukocyte antigen-G are demonstrated and the role of HLA-G as an immune regulator of GVHD is highlighted, which could also serve as a good predictor of GvHD and represent a new therapeutic target for GV HD.

New approaches in graft versus host disease (GvHD) management

  • J. Clausen
  • Biology, Medicine
    memo - Magazine of European Medical Oncology
  • 2016
Developments toward better, more individualized GVHD prophylaxis are needed, and one such emerging risk factor is the homozygosity for HLA-C group 1 killer cell immunoglobulin-like receptor (KIR) ligands.

Graft Immune Cell Composition Associates with Clinical Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with AML

There is considerable variation in the levels of immune cell populations between HSCT grafts, and this variation is associated with outcomes of HSCT in AML patients.

Understanding graft-versus-host disease. Preliminary findings regarding the effects of exercise in affected patients.

Although exercise training as an adjunct therapy to improve health outcomes after allo-HSCT shows promise (particularly, this lifestyle intervention can improve physical fitness and possibly immune function while attenuating fatigue), there is a need for more randomized control trials that focus on GVHD.

Plasma vascular non-inflammatory molecule 3 is associated with gastrointestinal acute graft-versus-host disease in mice

It is demonstrated that plasma VNN3 protein is associated with GI aGVHD in murine model after allogeneic HSCT.



Donor and host B cell‐derived IL‐10 contributes to suppression of graft‐versus‐host disease

It is demonstrated that host and donor B cell‐derived IL‐10 provides a unique mechanism of suppression of acute GvHD, and it is suggested that DCs are the targets of this B cell-mediated suppressive effect.

Prevention of acute graft‐versus‐host disease by humanized anti‐CD26 monoclonal antibody

Data indicate a role for CD26 in the regulation of GVHD and point to CD26 as a novel target for therapeutic intervention in this disease.

c‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice

It is reported here that T cells deficient for c‐Rel have a dramatically reduced ability to cause acute GVHD after allogeneic bone marrow transplantation using major and minor histocompatibility mismatched murine models, and that c‐ Rel can be a potential target for therapeutic intervention in allogeneIC hematopoietic cell transplantation in the clinic.

Third‐party Tolerogenic Dendritic Cells Reduce Allo‐reactivity In vitro and Ameliorate the Severity of Acute graft‐Versus‐host Disease in Allo‐bone Marrow Transplantation

Third‐party tDCs play a crucial role in reducing the severity of aGVHD by modulating the secretion of various cytokines and expanding Foxp3+ regulatory T cells, which suggests the possibility of using third‐party dendritic cells for therapeutic applications.

Cytokines in Graft-versus-Host Disease

The knowledge of the role that cytokines play in orchestrating GVHD is expanding rapidly and parallels other infective and inflammatory conditions in which a predominant T cell signature is causative of pathology.

Programmed Death-1 Pathway in Host Tissues Ameliorates Th17/Th1-Mediated Experimental Chronic Graft-versus-Host Disease

The results suggest that the PD-1 pathway contributes to the suppression of Th17/Th1-mediated chronic GVHD and may represent a new target for the prevention or treatment of chronicGVHD.

Targeting the IL17 pathway for the prevention of graft-versus-host disease.

Blockade of individual Notch ligands and receptors controls graft-versus-host disease.

It is demonstrated that notch1/Notch2 receptors and the Notch ligands Delta-like1/4 mediate all the effects of Notch signaling in T cells during GVHD, with dominant roles for Notch1 and Delta- like4.

The Role of Pattern-Recognition Receptors in Graft-Versus-Host Disease and Graft-Versus-Leukemia after Allogeneic Stem Cell Transplantation

A better understanding of the molecular mechanisms that govern GVHD versus GVL is urgently needed, which may ultimately allow to design modulators, which protect from GvHD but preserve donor T-cell attack on hematologic malignancies.