2026-03-12 カロリンスカ研究所（KI）
Photo: Pepifoto
＜関連情報＞
- https://news.ki.se/the-uterus-immune-system-can-regenerate-after-transplantation
- https://www.science.org/doi/10.1126/scitranslmed.adp2583
子宮または造血幹細胞移植後の子宮免疫環境の再構築 Reconstitution of the uterine immune milieu after uterus or hematopoietic stem cell transplantation
Benedikt Strunz, Martin A. Ivarsson, Dan Sun, Corinna Mayer, […] , and Niklas K. Björkström
Science Translational Medicine Published:11 Mar 2026
Editor’s summary
The human uterus cyclically remodels and sheds its lining, the endometrium, taking with it uterine immune cells, which are critical for implantation receptivity and spiral artery remodeling. It is not clear from where uterine immune cells are reconstituted nor what those cells contribute to disorders of pregnancy like preeclampsia. In a pair of papers, Strunz et al. and Asiimwe et al. studied small numbers of immunosuppressed recipients of uterus transplant (UTx) to gain insights into uterine immune biology. Strunz et al. studied endometrial and decidual samples collected after surgery from recipients of UTx and menstrual samples from recipients of hematopoietic stem cell transplantation, finding that uterine immune cells repopulated from the blood and with near-complete reconstitution of all immune cell lineages despite tacrolimus-induced reduction of NFAT (nuclear factor of activated T cells) signaling. Asiimwe et al. noted a reduction in uterine natural killer (uNK) cells in recipients of UTx that was associated with histopathologic evidence of maternal vascular malperfusion in decidual samples. Their further workup identified NFAT-induced transcriptional programs in uNK cells associated with tissue residency that were reduced by tacrolimus, suggesting a potential link between uNK cells and disorders of pregnancy. An accompanying Focus article by Molina-Vidales and colleagues puts these findings into perspective, along with open questions still needing answers. —Melissa L. Norton
Abstract
Maintenance of tissue-specific immunity is important for immunological fitness, but its establishment has been difficult to assess in humans. Here, we investigated reconstitution of the human uterine immune system by studying women who underwent uterus solid organ transplantation or hematopoietic stem cell transplantation (HSCT). Through single-cell identification based on single-nucleotide polymorphisms and disparate human leukocyte antigen expression using single-cell RNA sequencing or high-parameter flow cytometry, donor versus recipient cell origin was determined, and we examined the gene expression states, surface marker profiles, and spatial organization of these cells in the endometrium. Endometrial immune cell reconstitution occurred after both uterus transplant and HSCT at the transcriptomic, phenotypic, and spatial levels. Reconstitution involved restoration of all major immune lineages with frequencies comparable to those of healthy controls, with preservation of canonical endometrial immune architecture. Recipient-derived immune cells replaced donor immune cells after uterus transplant, whereas HSCT resulted in near-complete donor-derived immune reconstitution, including formation of tissue-resident lymphocytes. This occurred despite tacrolimus-induced, calcineurin-mediated inhibition of the nuclear factor of activated T cells (NFAT) pathway, which affected de novo induction of tissue-residency features in vitro. In one patient, immune cells of male origin reconstituted the endometrium after HSCT. Collectively, these data provide insights into tissue immune system persistence and reconstitution capabilities in the uterus, an organ that undergoes continuous regeneration.
