Peritoneal macrophages and exosomes in endometriosis

Endometriosis is a disease that affects up to 10% of women, causing chronic pelvic and period associated pain, and is associated with an increased incident of infertility. The disease is defined by the growth of lesions resembling the endometrium (inner layer of the uterus) outside the uterus on organs in the peritoneal cavity. The behavior of the immune system is critical both for allowing the establishment of these lesions, and in causing chronic inflammation that is responsible for many symptoms of the disease. Exosomes are membrane particles released from cells that may affect surrounding or distant cells. In this study, we want to understand the role that exosomes play in endometriosis by affecting immune cells and endometriosis lesions. To do that, we will first precisely identify and characterize the cells in the local immune environment in the peritoneal cavity that respond to endometriosis using CITE-seq on patient samples of peritoneal fluid. The CITE-seq is a technology that simultaneously assesses gene expression and immune cell antibody markers in individual cells. This will give the most complete picture to date of the composition of the local immune cell population most relevant to endometriosis, helping to better understand the disease and opening avenues for further research into possible treatments. Using the antibody marker gene combinations identified by CITE-seq, we will devise a strategy to isolate specific immune cell sub-populations that respond to endometriosis. We will focus on macrophages, an immune cell type that we and others have previously shown to be important in endometriosis. We will isolate exosomes from both macrophages and endometriosis lesions from patients samples, and conduct a series of experiments to determine if these exosomes have an effect on the disease. Differentiation of macrophages from one type to another is important for their function and relevant for a disease like endometriosis where they play a role. We will assess if exosomes from endometriosis lesions can affect macrophage differentiation and thereby influence the disease. Conversely, we will examine the effect of exosomes from different types of macrophages using disease models that resembles the normal and endometriosis state. These experiments will reveal the role of exosomes in endometriosis, and show which macrophage populations are important in the disease.