Functional Impairment of Activated Regulatory T Cells as a Central Immunological Defect in Endometriosis

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.

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.

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.

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.