A hypothesised factor in endometriosis onset is a local immune system dysfunction which not only fails to eliminate ectopic cells, but potentially aids lesion formation (1). Supporting this hypothesis, abnormal immune profiles have been observed in peritoneal fluid of endometriosis patients (2). This raises the question as to whether these abnormal profiles are simply due to the consistent presence of endometrial cells in the peritoneal cavity or, if not, whether an immune dysfunction could lead to the immune profiles observed (3).
In this work, we present a mathematical model of the immune cell interaction with endometrial cells in peritoneal fluid. As altered macrophage and natural killer cell behaviours are commonly implicated in endometriosis (3), we focus on these cell types in our model. Using our mathematical model, we determine the conditions under which endometrial cells do or do not persist as lesions. In particular, we address three hypotheses that could contribute to altered immune profiles: decreased detection of endometrial cells by immune cells, decreased clearance of endometrial cells by immune cells, and increased endometrial cell influx.
Our model predicts that an increased influx of endometrial cells into the system is associated with an increase in inflammation and immune activation, but is not associated with increased disease. Decreased clearance has a more significant effect on disease than decreased detection and is associated with an increase in inflammation and immune cell activation.
Consequently, our model predicts that, while an increase in endometrial influx could contribute to altered immune states in the case of no immune dysfunction, of the three hypotheses, a decrease in clearance of endometrial cells by the immune system is most strongly associated with both disease and an altered immune state.