摘要
Endometriosis is an estrogen-dependent inflammatory disease.The anti-inflammatory cytokine IL-10 also increased in endometriosis.However,the mechanism for origination and role of IL-10 in endometriosis was still large unknown.Here we report IL-10~+Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis,along with elevation of IL-27,IL-6 and TGF-β.Compared to peripheral CD4~+ T,endometrial CD4~+T highly expressed IL-27 receptors,especially ectopic endometrium.Under external(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD) and local(estrogen,IL-6 and TGF-β) environmental regulation,IL-27 from macrophage and endometrial stromal cells(ESC) induces IL-10 produce in Th17 cells in vitro and in vivo.This process is mediated through the interaction between c-musculoaponeuroticfibrosarconma(c-Maf) and retinoic acid-related orphan receptor gamma t(RORγt),and associated with the up-regulation of downstream B lymphocyte-induced maturation protein-1(Blimp-1).Such IL-10~+Th17 cells in turn stimulate the proliferation and implantation of ectopic lesion and accelerate the progress of endometriosis.These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 to produce IL-10 and promote rapid growth and implantation of ectopic lesion.This provides a scientific basis on which potential therapeutic strategies targeted to prevent the development of endometriosis,especially for patient with high level of IL-10~+Th17 cells.
Endometriosis is an estrogen-dependent inflammatory disease.The anti-inflammatory cytokine IL-10 also increased in endometriosis.However,the mechanism for origination and role of IL-10 in endometriosis was still large unknown.Here we report IL-10~+Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis,along with elevation of IL-27,IL-6 and TGF-β.Compared to peripheral CD4~+ T,endometrial CD4~+T highly expressed IL-27 receptors,especially ectopic endometrium.Under external(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD) and local(estrogen,IL-6 and TGF-β) environmental regulation,IL-27 from macrophage and endometrial stromal cells(ESC) induces IL-10 produce in Th17 cells in vitro and in vivo.This process is mediated through the interaction between c-musculoaponeuroticfibrosarconma(c-Maf) and retinoic acid-related orphan receptor gamma t(RORγt),and associated with the up-regulation of downstream B lymphocyte-induced maturation protein-1(Blimp-1).Such IL-10~+Th17 cells in turn stimulate the proliferation and implantation of ectopic lesion and accelerate the progress of endometriosis.These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 to produce IL-10 and promote rapid growth and implantation of ectopic lesion.This provides a scientific basis on which potential therapeutic strategies targeted to prevent the development of endometriosis,especially for patient with high level of IL-10~+Th17 cells.
引文