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在异种移植中诱导自然杀伤细胞耐受的策略。

Strategies to induce natural killer cell tolerance in xenotransplantation.

机构信息

Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States.

出版信息

Front Immunol. 2022 Aug 22;13:941880. doi: 10.3389/fimmu.2022.941880. eCollection 2022.

DOI:10.3389/fimmu.2022.941880
PMID:36072599
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9441937/
Abstract

Eliminating major xenoantigens in pig cells has drastically reduced human antibody-mediated hyperacute xenograft rejection (HXR). Despite these advancements, acute xenograft rejection (AXR) remains one of the major obstacles to clinical xenotransplantation, mediated by innate immune cells, including macrophages, neutrophils, and natural killer (NK) cells. NK cells play an 'effector' role by releasing cytotoxicity granules against xenogeneic cells and an 'affecter' role on other immune cells through cytokine secretion. We highlight the key receptor-ligand interactions that determine the NK cell response to target cells, focusing on the regulation of NK cell activating receptor (NKG2D, DNAM1) and inhibitory receptor (KIR2DL1-4, NKG2A, and LIR-1) signaling pathways. Inhibition of NK cell activity may protect xenografts from cytotoxicity. Recent successful approaches to reducing NK cell-mediated HXR and AXR are reviewed, including genetic modifications of porcine xenografts aimed at improving pig-to-human compatibility. Future directions to promote xenograft acceptance are discussed, including NK cell tolerance in pregnancy and NK cell evasion in viral infection.

摘要

消除猪细胞中的主要异种抗原大大降低了人类抗体介导的异种移植物超急性排斥反应（HXR）。尽管取得了这些进展，但急性异种移植物排斥反应（AXR）仍然是临床异种移植的主要障碍之一，由先天免疫细胞介导，包括巨噬细胞、中性粒细胞和自然杀伤（NK）细胞。NK 细胞通过释放细胞毒性颗粒对异种细胞发挥“效应器”作用，并通过细胞因子分泌对其他免疫细胞发挥“影响者”作用。我们强调了决定 NK 细胞对靶细胞反应的关键受体-配体相互作用，重点关注 NK 细胞激活受体（NKG2D、DNAM1）和抑制受体（KIR2DL1-4、NKG2A 和 LIR-1）信号通路的调节。抑制 NK 细胞活性可能会保护异种移植物免受细胞毒性。我们综述了最近减少 NK 细胞介导的 HXR 和 AXR 的成功方法，包括针对改善猪与人相容性的猪异种移植物的基因修饰。讨论了促进异种移植物接受的未来方向，包括妊娠中的 NK 细胞耐受和病毒感染中的 NK 细胞逃逸。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/9441937/0b2bad9cdfd9/fimmu-13-941880-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/9441937/00b43dc69a54/fimmu-13-941880-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/9441937/763759e695e4/fimmu-13-941880-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/9441937/0b2bad9cdfd9/fimmu-13-941880-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/9441937/00b43dc69a54/fimmu-13-941880-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/9441937/763759e695e4/fimmu-13-941880-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/9441937/0b2bad9cdfd9/fimmu-13-941880-g003.jpg

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本文引用的文献

1
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2
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Front Immunol. 2022 Mar 28;13:858604. doi: 10.3389/fimmu.2022.858604. eCollection 2022.
3
Early Interferon-Gamma Response in Nonhuman Primate Recipients of Solid-Organ Xenotransplantation.实体器官异种移植中非人类灵长类动物受者的早期干扰素-γ反应。
临床异种移植中感染的监测与预防
Clin Microbiol Rev. 2025 Mar 13;38(1):e0015023. doi: 10.1128/cmr.00150-23. Epub 2025 Jan 31.
4
Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.β 细胞替代治疗中的免疫保护策略：深入探讨猪胰岛异种移植。
Adv Sci (Weinh). 2024 Aug;11(31):e2401385. doi: 10.1002/advs.202401385. Epub 2024 Jun 17.
5
Developments in kidney xenotransplantation.肾异种移植的进展。
Front Immunol. 2024 Jan 11;14:1242478. doi: 10.3389/fimmu.2023.1242478. eCollection 2023.
6
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Cells. 2023 Nov 7;12(22):2587. doi: 10.3390/cells12222587.
7
Co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells attenuates human NK cell-mediated degranulation.基因修饰猪内皮细胞共表达 HLA-E 和 HLA-G 可减弱人 NK 细胞介导的脱颗粒作用。
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