Dataset Information

Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation.

ABSTRACT: Organ transplantation is a lifesaving option for patients with advanced diseases. Rejection is regarded as one of the most severe risk factors post-transplantation. A molecule that contributes to immune tolerance and resisting rejection is human leukocyte antigen (HLA)-G, which belongs to the non-classical major histocompatibility complex class (MHC) I family. HLA-G was originally found to play a role during pregnancy to maintain immune tolerance between mother and child. It is expressed in the placenta and detected in several body fluids as soluble factor as well as different membrane isoforms on cells. Recent findings on HLA-G show that it can also play multifaceted roles during transplantation. This review will explain the general characteristics and biological function of HLA-G and summarize the views supporting the tolerogenic and other roles of HLA-G to better understand its role in solid organ transplantation (SOT) and its complications. Finally, we will discuss potential future research on the role of HLA-G in prevention, diagnosis, and treatment in SOT.

SUBMITTER: Liu S

PROVIDER: S-EPMC9234285 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation.

Liu Siqi S Bos Nicolaas A NA Verschuuren Erik A M EAM van Baarle Debbie D Westra Johanna J

Frontiers in immunology 20220613

Organ transplantation is a lifesaving option for patients with advanced diseases. Rejection is regarded as one of the most severe risk factors post-transplantation. A molecule that contributes to immune tolerance and resisting rejection is human leukocyte antigen (HLA)-G, which belongs to the non-classical major histocompatibility complex class (MHC) I family. HLA-G was originally found to play a role during pregnancy to maintain immune tolerance between mother and child. It is expressed in the ...[more]

PMID: 35769475

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Project description:Graft rejection remains the major obstacle after vascularized solid organ transplantation. Endothelial cells, which form the interface between the transplanted graft and the host's immunity, are the first target for host immune cells. During acute cellular rejection endothelial cells are directly attacked by HLA I and II-recognizing NK cells, macrophages, and T cells, and activation of the complement system leads to endothelial cell lysis. The established forms of immunosuppressive therapy provide effective treatment options, but the treatment of chronic rejection of solid organs remains challenging. Chronic rejection is mainly based on production of donor-specific antibodies that induce endothelial cell activation-a condition which phenotypically resembles chronic inflammation. Activated endothelial cells produce chemokines, and expression of adhesion molecules increases. Due to this pro-inflammatory microenvironment, leukocytes are recruited and transmigrate from the bloodstream across the endothelial monolayer into the vessel wall. This mononuclear infiltrate is a hallmark of transplant vasculopathy. Furthermore, expression profiles of different cytokines serve as clinical markers for the patient's outcome. Besides their effects on immune cells, activated endothelial cells support the migration and proliferation of vascular smooth muscle cells. In turn, muscle cell recruitment leads to neointima formation followed by reduction in organ perfusion and eventually results in tissue injury. Activation of endothelial cells involves antibody ligation to the surface of endothelial cells. Subsequently, intracellular signaling pathways are initiated. These signaling cascades may serve as targets to prevent or treat adverse effects in antibody-activated endothelial cells. Preventive or therapeutic strategies for chronic rejection can be investigated in sophisticated mouse models of transplant vasculopathy, mimicking interactions between immune cells and endothelium.

Dataset Information

Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation.

Publications

Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation.

Similar Datasets

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