Speaker
Description
The endometrial cycle is known to be mediated via the endocrine system, with both estradiol and progesterone hormones heavily implicated in menstruation. Throughout this cycle, the tissue undergoes vast changes in tissue and cellular-level function, including phagocytosis and apoptosis, cell proliferation, both tissue and vascular remodelling, and extracellular matrix construction. Macrophages are a key component of the regulation of these vastly different function, and have traditionally thought of as either M1-like (pro-inflammatory) phenotype, or M2-like (anti- inflammatory) phenotype. However, a paradigm shift is underway, where macrophages are increasingly observed to exhibit characteristics of each phenotype simultaneously. This is referred to as the “continuum spectrum of Macrophage phenotypes”.
In this work, we present a mathematical model of a continuous macrophage phenotype. We utilise openly available, single cell transcriptomics data, and the fact that the endocrine system is a driver of endometrial cycle dynamics, to validate our model. This validated models allows us to understand how the macrophages change their phenotype along this continuous spectrum throughout the hormonal cycle. We then use our validated model for hypothesis generation, in the context of immune dysfunction and its potential consequences, for example for the uterine disease endometriosis.
