Endometriosis is a chronic inflammatory, hormone dependent disorder that affects more than 200 million women worldwide. Immune dysfunction has emerged as one of the predominant mechanisms facilitating endometriosis lesion growth and survival. In particular, T cell subsets are predominant effector immune cells within the complex endometriosis lesion microenvironment. T cell biology encompasses a highly regulated and diverse network of cellular differentiation, antigen recognition, and immune regulation, all of which play critical roles in immune homeostasis. This complexity becomes particularly relevant in endometriosis, as autologous lesions evade immune clearance within this sterile, non-pathogen-driven inflammatory milieu, highlighting a failure of immune surveillance and debris clearance. Indeed, aberrant T cell phenotypes, including skewed Th2 and regulatory subsets, promote an anti-inflammatory and tissue-remodeling environment in endometriosis. Despite advances in characterizing immune cell subsets, the mechanisms underlying T cell dysfunction and lesion persistence remain poorly defined. Here, we provide comprehensive insights into the diverse T cell subsets infiltrating endometriosis lesions and associated mechanisms that potentially contribute to endometriosis lesion establishment and subsequent survival. A systems-level understanding of T cell roles within the endocrine-immune microenvironment is essential for developing targeted immunotherapies and personalized interventions for this globally prevalent disease.
Sisnett et al. (Wed,) studied this question.