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免疫系统与人类肾脏类器官的相互作用。

Interactions of the Immune System with Human Kidney Organoids.

作者信息

Shankar Anusha S, Tejeda-Mora Hector, Du Zhaoyu, Nlandu Quincy, Palomares-Cabeza Virginia, van den Bosch Thierry P P, Korevaar Sander S, Da Costa Gonçalves Fabiany, Bindels Eric M J, Kramann R, Reinders Marlies E J, Clahsen-van Groningen Marian C, Hoorn Ewout J, Gribnau Joost, Baan Carla C, Hoogduijn Martin J

机构信息

Department of Internal Medicine, Erasmus MC, Erasmus MC Transplant Institute, University Medical Center, Rotterdam, Netherlands.

Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center, Rotterdam, Netherlands.

出版信息

Transpl Int. 2024 Apr 18;37:12468. doi: 10.3389/ti.2024.12468. eCollection 2024.

DOI:10.3389/ti.2024.12468
PMID:38699175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11064018/
Abstract

Kidney organoids are an innovative tool in transplantation research. The aim of the present study was to investigate whether kidney organoids are susceptible for allo-immune attack and whether they can be used as a model to study allo-immunity in kidney transplantation. Human induced pluripotent stem cell-derived kidney organoids were co-cultured with human peripheral blood mononuclear cells (PBMC), which resulted in invasion of allogeneic T-cells around nephron structures and macrophages in the stromal cell compartment of the organoids. This process was associated with the induction of fibrosis. Subcutaneous implantation of kidney organoids in immune-deficient mice followed by adoptive transfer of human PBMC led to the invasion of diverse T-cell subsets. Single cell transcriptomic analysis revealed that stromal cells in the organoids upregulated expression of immune response genes upon immune cell invasion. Moreover, immune regulatory PD-L1 protein was elevated in epithelial cells while genes related to nephron differentiation and function were downregulated. This study characterized the interaction between immune cells and kidney organoids, which will advance the use of kidney organoids for transplantation research.

摘要

肾类器官是移植研究中的一种创新工具。本研究的目的是调查肾类器官是否易受同种免疫攻击，以及它们是否可作为研究肾移植同种免疫的模型。将人诱导多能干细胞衍生的肾类器官与人外周血单个核细胞（PBMC）共培养，结果导致同种异体T细胞侵入肾单位结构周围以及类器官基质细胞区室中的巨噬细胞。这一过程与纤维化的诱导有关。在免疫缺陷小鼠皮下植入肾类器官，随后过继转移人PBMC，导致多种T细胞亚群的侵入。单细胞转录组分析显示，免疫细胞侵入后，类器官中的基质细胞上调了免疫反应基因的表达。此外，上皮细胞中免疫调节性PD-L1蛋白升高，而与肾单位分化和功能相关的基因下调。本研究对免疫细胞与肾类器官之间的相互作用进行了表征，这将推动肾类器官在移植研究中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/11c8d290afbd/ti-37-12468-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/c5551b09cfc1/ti-37-12468-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/09a082cbd2f6/ti-37-12468-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/a24fbb349423/ti-37-12468-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/81ba08e1f417/ti-37-12468-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/2a6568e90d51/ti-37-12468-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/11c8d290afbd/ti-37-12468-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/c5551b09cfc1/ti-37-12468-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/5ca6de4bede0/ti-37-12468-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/09a082cbd2f6/ti-37-12468-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/a24fbb349423/ti-37-12468-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/81ba08e1f417/ti-37-12468-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/2a6568e90d51/ti-37-12468-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fe/11064018/11c8d290afbd/ti-37-12468-g007.jpg

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Cross-tissue immune cell analysis reveals tissue-specific features in humans.跨组织免疫细胞分析揭示人类组织特异性特征。
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SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids.SARS-CoV-2 感染人类肾脏并导致肾类器官纤维化。
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