Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Abstract

Endometriosis is defined as the presence of endometrial-like glands and stroma located outside the uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% of reproductive-aged women and is a well-recognized cause of chronic pelvic pain and infertility. Despite the still unknown etiology of endometriosis, much evidence suggests the participation of epigenetic mechanisms in the disease etiopathogenesis. The main rationale is based on the fact that heritable phenotype changes that do not involve alterations in the DNA sequence are common triggers for hormonal, immunological, and inflammatory disorders, which play a key role in the formation of endometriotic foci. Epigenetic mechanisms regulating T-cell responses, including DNA methylation and posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work in concert with organ structural cells to generate appropriate immune responses and are functionally shaped by organ-specific environmental conditions. Thus, a failure to precisely regulate immune cell transcription may result in compromised immunological integrity of the organ with an increased risk of inflammatory disorders. The coexistence of endometriosis and autoimmunity is a well-known occurrence. Recent research results indicate regulatory T-cell (Treg) alterations in endometriosis, and an increased number of highly active Tregs and macrophages have been found in peritoneal fluid from women with endometriosis. Elimination of the regulatory function of T cells and an imbalance between T helper cells of the Th1 and Th2 types have been reported in the endometria of women with endometriosis-associated infertility. This review aims to present the state of the art in recognition epigenetic reprogramming of T cells as the key factor in the pathophysiology of endometriosis in the context of T-cell-related autoimmunity. The new potential therapeutic approaches based on epigenetic modulation and/or adoptive transfer of T cells will also be outlined.

The role of CD8+ T cells in endometriosis: a systematic review

“…In endometriosis, an increased ratio of altered peritoneal macrophages has been indicated, and since they are involved in antigen presentation to CD8 T cells, this points to potentially related dysfunctions within the CD8 T cell compartment. Similarly, changes were found in regulatory T cells (Tregs) in endometriosis, with findings showing an increased number of activated Tregs in the peritoneal fluid of patients with endometriosis ( 93 ). Like macrophages, Tregs are involved in CD8 T cell activation and play an important role in the generation of high-avidity initial responses and effective memory ( 94 ).…”

Cross-Talk between N6-Methyladenosine and Their Related RNAs Defined a Signature and Confirmed m6A Regulators for Diagnosis of Endometriosis

“…Through Pearson analysis, we discovered 25 m6A-regulated mRNAs. Recent studies have demonstrated the impact of SCG2 on the clinical stage, and the influence of macrophage polarization on immunotherapy in colorectal cancer [ 18 , 19 ]. GPC3 [ 20 ] has also been proven to be essential in the immune response, yet no reference has been reported in EM.…”

Molecular Mechanisms of the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

“…Epigenetic factors are mediators of inflammation and chronic inflammatory disease. Consistently, a disruption of immune cell epigenetic regulation is thus predicted to be a major contributor to unrestrained immune responses and immune tolerance disruption that lead to diseases such as autoimmunity and inflammation [259][260][261]. These epigenetic changes can be caused by smoking, exposure to chemicals, including endocrine-disrupting compounds (EDCs), in the environment, or diet and other lifestyle factors, including sedentary behavior.…”