Innate Cellular Immunity in Xenotransplantation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 27 June 2024 | Viewed by 1520

Special Issue Editor

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Guest Editor
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
Interests: genome editing; xenotransplantation; immune tolerance; 3D-organoid culture; natural killer cells

Special Issue Information

Dear Colleagues,

Xenotransplantation, cross-species transplantation, is a promising solution to human organ shortage. Recent advancements in the genetic engineering of pigs to improve pig–human compatibility has brought us closer to achieving successful xenotransplantation. Human antibody-mediated hyperacute rejection can be effectively prevented by eliminating xenoantigens on porcine xenograft. However, immune-cell-mediated xenograft rejection remains a barrier for the application of xenotransplantation in the clinic. Innate immune cells including natural killer cells, macrophages, dendritic cells, and neutrophils contribute to xenograft destruction. To achieve a long-term porcine xenograft survival in humans, inhibiting the activation of human innate immune cell is crucial.

This Special Issue seeks to publish original research and review articles on the mechanisms of human innate immune cell activation to porcine cell stimulation, novel strategies to promote local innate immune tolerance via the genetic engineering of pigs (through the addition of human inhibitory molecules and “markers of self”, and the elimination of porcine activation molecules), and the current status of immunosuppressive agents on innate immune response in xenotransplantation.

Dr. Ping Li
Guest Editor

Manuscript Submission Information

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  • innate immunity
  • natural killer cells
  • microphages
  • dendritic cells
  • neutrophils
  • xenotransplantation
  • immune rejection
  • immune tolerance
  • xenograft
  • genetic engineering

Published Papers (1 paper)

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11 pages, 4508 KiB  
Porcine UL-16 Binding Protein 1 Is Not a Functional Ligand for the Human Natural Killer Cell Activating Receptor NKG2D
by Kevin J. Lopez, John Paul Spence, Wei Li, Wenjun Zhang, Barry Wei, Arthur A. Cross-Najafi, James R. Butler, David K. C. Cooper, Burcin Ekser and Ping Li
Cells 2023, 12(22), 2587; - 7 Nov 2023
Cited by 1 | Viewed by 1211
Natural killer (NK) cells play a vital role in xenotransplantation rejection. One approach to induce NK cell immune tolerance is to prevent the NK cell-mediated direct killing of porcine cells by targeting the interaction of the activating receptor NKG2D and its ligands. However, [...] Read more.
Natural killer (NK) cells play a vital role in xenotransplantation rejection. One approach to induce NK cell immune tolerance is to prevent the NK cell-mediated direct killing of porcine cells by targeting the interaction of the activating receptor NKG2D and its ligands. However, the identity of porcine ligands for the human NKG2D receptor has remained elusive. Previous studies on porcine UL-16 binding protein 1 (pULBP-1) as a ligand for human NKG2D have yielded contradictory results. The goal of the present study was to clarify the role of pULBP-1 in the immune response and its interaction with human NKG2D receptor. To accomplish this, the CRISPR/Cas9 gene editing tool was employed to disrupt the porcine ULBP-1 gene in a 5-gene knockout porcine endothelial cell line (GGTA1, CMAH, β4galNT2, SLA-I α chain, and β-2 microglobulin, 5GKO). A colony with two allele mutations in pULBP-1 was established as a 6-gene knockout pig cell line (6GKO). We found that pULBP-1-deficient pig cells exhibited a reduced binding capacity to human NKG2D-Fc, a recombinant chimera protein. However, the removal of ULBP-1 from porcine endothelial cells did not significantly impact human NK cell degranulation or cytotoxicity upon stimulation with the pig cells. These findings conclusively demonstrate that pULBP-1 is not a crucial ligand for initiating xenogeneic human NK cell activation. Full article
(This article belongs to the Special Issue Innate Cellular Immunity in Xenotransplantation)
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