Exacerbation of endometriosis due to regulatory t-cell dysfunction

Abstract

Context: Endometriosis is a chronic inflammatory disease associated with altered immune response to endometrial cells facilitating the implantation and proliferation of ectopic endometrial tissues. Although regulatory T (Treg) cells play a key role in T cell-mediated immune response and development of immune disorders, their significance in endometriosis remains to be elucidated. Recently, CD4+CD45RA2 forkhead box protein 3 (Foxp3)hi T cells, activated Treg cells, have been identified as a functionally true suppressive population of Treg cells. Objective: To investigate the role of Treg cells in endometriosis. Design: Three Treg cell fractions (resting Treg cells, activated Treg cells, and non-Treg cells) were examined using flowcytometry in the endometrioma, endometrium, peritoneal fluid, and peripheral blood obtained from women with (n = 27) and without (n = 28) endometriosis. A mouse model of endometriosis was made in Foxp3tm3Ayr/J (Foxp3DTR) C57BL/6 Treg cell-depleted mice (n = 28). Results: In women with endometrioma, the proportion of activated Treg cells in the endometrioma and the endometrium, but not in the peritoneal fluid or peripheral blood, was significantly decreased compared with that in women without endometriosis. In Foxp3DTR/diphtheria toxin mice, the number and weight of endometriotic lesions, inflammatory cytokine levels and angiogenetic factors were significantly increased compared with those in control mice. Conclusions: Treg cell deficiency exaggerates local inflammation and angiogenesis and simultaneously facilitates the attachment and growth of endometrial implants. The findings provide an insight into dysregulated immune response for the pathogenesis and development.