The Immunopathophysiology of Endometriosis

Immunological dysfunction, involving defective immunosurveillance against autologous tissue deposited in the peritoneal cavity, facilitates endometriotic lesion growth in endometriosis patients and ultimately perpetuates disease symptoms. Conversely, innate and adaptive immune cells from endometriosis patients produce several proinflammatory and blood vessel growth-promoting factors that contribute to hallmarks of disease pathophysiology. Persistent and prolonged endometriosis-associated inflammation further contributes to comorbidities. Recent studies suggest that endometriotic lesions harbor a unique microenvironment. The interplay between immune cells with stromal and epithelial compartments of lesions is regulated by hormonal pathways. Targeting dysregulated immune pathways represents a potential avenue for novel therapeutic development that will hopefully not impact fertility. Endometriosis is a chronic, inflammatory, estrogen-dependent disease characterized by the growth of endometrial tissue outside of the uterine cavity. Although the etiology of endometriosis remains elusive, immunological dysfunction has been proposed as a critical facilitator of ectopic lesion growth following retrograde menstruation of endometrial debris. However, it is not clear whether this immune dysfunction is a cause or consequence of endometriosis. Thus, here we provide in-depth insights into our current understanding of the immunopathophysiology of endometriosis and highlight challenges and opportunities for future research. With the explosion of successful immune-based therapies targeting various chronic inflammatory conditions, it is crucial to determine whether immune dysfunction can be therapeutically targeted in endometriosis. Endometriosis is a chronic, inflammatory, estrogen-dependent disease characterized by the growth of endometrial tissue outside of the uterine cavity. Although the etiology of endometriosis remains elusive, immunological dysfunction has been proposed as a critical facilitator of ectopic lesion growth following retrograde menstruation of endometrial debris. However, it is not clear whether this immune dysfunction is a cause or consequence of endometriosis. Thus, here we provide in-depth insights into our current understanding of the immunopathophysiology of endometriosis and highlight challenges and opportunities for future research. With the explosion of successful immune-based therapies targeting various chronic inflammatory conditions, it is crucial to determine whether immune dysfunction can be therapeutically targeted in endometriosis. arm of the immune system consisting of T and B lymphocytes that is highly specific and responsible for immunological memory. type of macrophage involved in wound healing and tissue repair that is activated by exposure to certain cytokines such as IL-4, IL-10, or IL-13. the development of new blood vessels from pre-existing vessels through sprouting or intussusception. Angiogenic growth factors include the vascular endothelial growth factor (VEGF) family, angiopoietins (Ang 1/2), fibroblast growth factor (FGF), platelet-derived growth factor-B (PDGF-B), cytokines, and chemokines. also known as an immunoglobulin, is a protein produced by a class of activated B cells called plasma cells of the immune system. These antibodies bind and neutralize antigens to remove them from the body. cells of the humoral adaptive immune system responsible for mediating the production of antibodies. class of cytokine proteins that are responsible for immune cell migration. type of macrophage that produces high levels of proinflammatory cytokines, mediates resistance to pathogens, and produces reactive nitrogen and oxygen intermediates. Interferon gamma and lipopolysaccharide (LPS) polarize macrophages toward the M1 phenotype. small proteins involved in signaling between cells and regulation of immune responses. host biomolecules that act as endogenous danger signals or alarmins to initiate or perpetuate the inflammatory response. innate immune cells that function to sample antigens within the surrounding environment and coordinate subsequent immune responses. DCs process and present antigens to naïve T cells, thereby providing an essential link between the innate and adaptive arms of the immune system. model of endometriosis in non-human primates in which an experimentally induced narrowing or obstruction of the cervix hinders the passage of menstrual debris between the uterus and vaginal canal. This results in increased retrograde menstruation and subsequent development of endometriotic lesions within the peritoneal cavity. a group of cytokines produced and secreted by a variety of lymphoid and non-lymphoid cells that are involved in inflammation and immune system regulation. critical sensor of the innate immune system that when activated, promotes caspase-1-mediated cleavage of the precursor cytokines pro-IL-1β and pro-IL-18 into their bioactive and proinflammatory forms. comprised of cells and pathways that provide a first line of defense against exogenous or endogenous danger signals. Innate immune responses are rapid and nonspecific in nature. a specialized innate phagocytic cell that plays an essential role in the clearance of cellular debris as well as in the release of both inflammatory and chemotactic immune effector molecules. lymphocytes with both innate and adaptive immune features. These cells possess constitutive cytotoxic and cytokine-producing abilities and can participate in rapid response to viral-infected cells and tumor immunosurveillance. short-lived innate immune cells that contain cytoplasmic granules and are rapidly recruited to sites of infection. Recent evidence has revealed emerging roles for neutrophils in cancer and chronic inflammatory conditions. CD4+ immune cells that express the IL-2 receptor alpha chain (CD25) and the transcription factor forkhead box protein P3 (FOXP3). Tregs function to regulate or suppress other cells of the immune system to control the immune response to self and foreign antigens. the flow of menstrual fluid backwards through the fallopian tubes into the peritoneal cavity instead of out of the body. adaptive immune cells responsible for cell-mediated immunity. These cells can recognize foreign antigens by specific cell surface receptors and release cytokines. T cells are further divided into subsets according to their function.