Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Informatics Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
Nat Commun. 2024 Apr 11;15(1):3140. doi: 10.1038/s41467-024-47454-7.
Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression may be able to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.
猪到人的异种移植正迅速进入临床领域；然而，尚不清楚哪种免疫调节方案将有效地控制人体对猪异种移植物的免疫反应。在这里，我们在药物免疫抑制的情况下将经过基因编辑的猪肾移植到脑死亡的人类受体中，并使用空间转录组学和单细胞 RNA 测序研究异种移植物的人体免疫反应。异种移植后早期，人类免疫细胞在猪肾皮质中很少见，主要由髓样细胞组成。猪固有巨噬细胞和人类浸润巨噬细胞均表达与替代激活、抗炎表型一致的基因。在猪肾异种移植物中未检测到明显的人类 B 或 T 细胞浸润。总的来说，这些发现提供了一个概念验证，即传统的药物免疫抑制可能能够限制在相容的猪到人类肾异种移植后早期人类免疫细胞浸润到异种移植物中。
