ABSTRACT Background Endometriosis is increasingly recognized as a disorder of impaired reproductive immune tolerance rather than solely an endocrine disease. Although previous studies have reported inconsistent findings regarding the number of regulatory T cells (Tregs), the functional integrity of distinct Treg subsets and their contribution to disease pathogenesis remains unclear. Methods We reviewed clinical, experimental, and translational studies focusing on regulatory T‐cell biology in endometriosis, with emphasis on functional Treg subsets, immune interactions within ectopic lesions, and emerging immunomodulatory therapeutic approaches. Main Findings Accumulating evidence indicates that endometriosis is characterized not by a reduction in total Foxp3 + Treg numbers but by a qualitative deficiency of activated regulatory T cells (aTregs). Local loss of aTregs in ectopic endometrium and ovarian endometrioma is associated with enhanced inflammatory and angiogenic activation, including increased IL‐6, CCL2, and VEGF production, macrophage activation, and dysregulated Th17 responses. Experimental studies using Treg‐depleted mouse models further demonstrate that impaired Treg‐mediated regulation accelerates lesion growth, whereas adoptive Treg transfer suppresses inflammation and disease progression. Conclusion Functional impairment of activated regulatory T cells represents a central immunological defect underlying chronic inflammation, lesion persistence, and infertility in endometriosis. Restoration of Treg‐mediated immune regulation may provide a promising nonhormonal, fertility‐preserving therapeutic strategy.
Tanaka et al. (Thu,) studied this question.