Fig. 10: Schematic diagram of this study.

In stage I–II endometriosis, the increased secretion of inflammatory cytokines in ectopic milieu induces FGL2 secretion in Tregs. sFGL2 induces pro-repair macrophages skewing through the suppression of NF-κB and the activation of SHP2-ERK1/2-STAT3 pathway. sFGL2 also up-regulates MT expression in macrophages through STAT3 activation which further promotes pro-repair macrophage polarization. In addition, sFGL2-induced pro-repair macrophages inhibit Th1 and Th17 cell differentiation, while promote Th2 and Tregs differentiation. Taken together, sFGL2 mediated cross-talk between Tregs and macrophage alters the balance of pro- and anti-inflammatory microenvironments and facilitates the formation of immune tolerance in stage III-IV endometriosis.