Miller Claire M, Germano Domenic P J, Chenoweth Alicia M, Holdsworth-Carson Sarah
Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia.
J R Soc Interface. 2025 Aug;22(229):20250076. doi: 10.1098/rsif.2025.0076. Epub 2025 Aug 13.
The immune system is hypothesized to contribute to the onset of endometriosis lesions. However, the precise mechanisms underlying its role are not yet known. We introduce a novel compartmental model that describes the interactions between innate immune cells, specifically macrophages and natural killer cells, and endometrial cells, occurring within the peritoneal fluid during the early stages of (superficial peritoneal) endometriosis lesion onset. Our study focuses on retrograde influx, immune detection and immune clearance. Results show an increased influx of endometrial cells into peritoneal fluid correlates with heightened pro-inflammatory macrophage activation, but does not lead to an increase in disease. We compare the system's response to changes in immune cytotoxicity and ability to detect ectopic endometrial cells. We predict that reduced cytotoxicity is a key driver of disease. These findings align with the increased immune activation observed clinically. Finally, we predict that an individual can transition to a diseased state following a reduction in immune system cytotoxicity and/or reduced ability to detect ectopic cells. Due to hysteresis, a significant improvement is then required to restore an individual to the disease-free state. This work provides a valuable framework to explore hypotheses of endometriosis lesion onset and assist in understanding of the disease.
免疫系统被认为与子宫内膜异位症病变的发生有关。然而，其作用的精确机制尚不清楚。我们引入了一种新型的分区模型，该模型描述了在（浅表腹膜）子宫内膜异位症病变发生的早期阶段，腹膜液中固有免疫细胞，特别是巨噬细胞和自然杀伤细胞与子宫内膜细胞之间的相互作用。我们的研究重点是逆行流入、免疫检测和免疫清除。结果表明，子宫内膜细胞流入腹膜液增加与促炎性巨噬细胞激活增强相关，但不会导致疾病增加。我们比较了该系统对免疫细胞毒性变化和检测异位子宫内膜细胞能力的反应。我们预测细胞毒性降低是疾病的关键驱动因素。这些发现与临床上观察到的免疫激活增加一致。最后，我们预测个体在免疫系统细胞毒性降低和/或检测异位细胞能力降低后可能转变为患病状态。由于滞后现象，需要显著改善才能使个体恢复到无病状态。这项工作为探索子宫内膜异位症病变发生的假说提供了一个有价值的框架，并有助于对该疾病的理解。
