Altered Immunity in Endometriosis: What Came First?

Abstract

This review confirms that despite decades of intensive research, the involvement of the immune system remains elusive, as we can recognize the changes, but still do not understand if these changes represent the results of endometriosis or if they are contributing factors. Based on these findings, we also discuss new treatment possibilities.

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis

“…Macrophages are the first defense line of the immune system, by removing pathogens through phagocytosis and cell debris through cytokine secretion (58). An elevated number of macrophages are found in endometriosis patients during all phases of the menstrual cycle (59).…”

“…Usually, there is a balance between populations of regulatory T-cells (T regs ), a subgroup of helper T cells (CD4+) that act as anti-inflammatory cells, and effector or cytotoxic T-cells (CD8+); this equilibrium is required to maintain immune tolerance and to eliminate endometriotic cells. However, the high levels of E2 and the reduced P4 response influence in the elevated concentration of T regs in peritoneal fluid and in the endometriotic lesions, which decrease immune surveillance (58) and suppress the immune response, promote in this way the establishment of lesions (69). In contrast, effector T cells show a decreased activity, while helper T-cells in general are increased and participate in secreting high levels of cytokines (58,70).…”

“…However, the high levels of E2 and the reduced P4 response influence in the elevated concentration of T regs in peritoneal fluid and in the endometriotic lesions, which decrease immune surveillance (58) and suppress the immune response, promote in this way the establishment of lesions (69). In contrast, effector T cells show a decreased activity, while helper T-cells in general are increased and participate in secreting high levels of cytokines (58,70). Growth of endometriotic lesions is allowed by reduced ratios of Th1 to Th2 cells, with the consequent potentiation of Th1 response, mainly in the first stages of disease (71,72).…”

“…Growth of endometriotic lesions is allowed by reduced ratios of Th1 to Th2 cells, with the consequent potentiation of Th1 response, mainly in the first stages of disease (71,72). The Th1/Th2 ratio depends on the stage of the disease once it has been established, since Th1 cytokines prevalence occurs during minimal to mild endometriosis whereas Th2 cytokines are manifested in severe stages (58). Besides, the Th17 cell subset has a role in endometriosis, mediated by secretion of IL-17 resulting in the secretion of chemokine (C-C motif) ligand 20 (CCL20; also known as macrophage inflammatory protein-3, MIP3A) by endometriotic cells.…”

In‑vitro models of human endometriosis (Review)

“…Since endometriosis is recognized as a chronic inflammatory disease, the immune response of endometriotic cells have been investigated in vitro. Although endometriotic cell lines are not immune cells, they can respond to many immune regulators by producing cytokines or regulating cell functions, which indicate the importance of the immune response in the process of endometriosis and the close involvement of endometriotic cells in this inflammatory reaction (11). For example, IL-33 stimulates the production of pro-inflammatory cytokines in 12-Z cells, including chemokine ligand (CXCL)1, IL-6, granulocyte-macrophage colony-stimulating factor and IL-15 (12) (Fig.…”