Aberrant NK Cell Migration and Differentiation Underlie Immune Dysregulation in Endometriosis 2259942

Abstract Introduction Endometriosis affects approximately 10% of women of reproductive age and remains a major clinical challenge due to its association with infertility and reduced quality of life. The disease is difficult both to diagnose and to treat, as current approaches–including laparoscopic removal and hormonal therapy–are time-consuming and often fail to achieve a complete cure. Previous studies have demonstrated impaired NK cell function in patients with endometriosis, while murine experiments have suggested a potential role for NK cells in disease regulation; however, the mechanisms underlying this dysfunction remain unclear. This study aims to investigate whether and how aberrant NK cell migration and differentiation contribute to immune dysregulation in endometriosis. Methods A murine endometriosis model induced by intraperitoneal injection of dissociated uterine horn tissue and spatial transcriptomic profiling of patient-derived lesions were utilized to characterize NK cell subsets and their transcriptional signatures within endometriotic tissues in mice and humans. Results Antibody-mediated NK cell depletion using an NK1.1 monoclonal antibody resulted in significantly larger lesions, indicating that NK cells contribute to lesion control. Moreover, lesion weight was negatively correlated with the abundance of tissue-resident NK cells. Using a congenic mouse model, we confirmed that CD49a+ tissue-resident NK cells were not derived from donor uteri, but originated from the host, suggesting that NK cell migration and differentiation are essential for their function in regulating lesion growth. Conclusion Ongoing studies are expanding on these preliminary findings to elucidate how NK cell migration and differentiation shape the immune landscape of endometriosis. A deeper understanding of these mechanisms may provide a foundation for developing novel diagnostic and therapeutic strategies targeting NK cell—mediated immune regulation. Funding Source This research was supported by a grant of the Boston-Korea Innovative Research Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. : RS-2024-00403047) Topic Categories Immune Mechanisms of Human Disease (HUM)