IMMUNOLOGY2024™ Conference Recordings-Critical role of NFAT in tissue residency transcriptional programming of human uterine natural killer cells

Critical role of NFAT in tissue residency transcriptional programming of human uterine natural killer cells

Video Transcription

Video Summary

This talk examined how uterine natural killer (NK) cells are programmed to become tissue-resident and how this may relate to preeclampsia in uterine transplant recipients. Using endometrial biopsies, single-cell sequencing, histology, and cell culture, the speaker found that uterine transplant patients had fewer NK cells overall, with the loss mainly affecting tissue-resident NKs, especially the TRNK3 subset. These cells also showed reduced expression of residency markers such as CD49A and CD103, suggesting altered tissue residency. The team proposed that immunosuppressive FK506 disrupts NFAT-dependent residency programming. Supporting this, a curated NFAT tissue-residency gene signature was downregulated in transplant NK cells. In culture, IL-15 increased TRNK3 cells, while FK506 blocked this effect, indicating IL-15 may trigger NFAT-dependent residency. The findings link defective NK residency with abnormal placentation and a possible preeclampsia risk.

Keywords

uterine natural killer cells

tissue-resident NK cells

preeclampsia

uterine transplant

FK506 NFAT signaling