子宫内膜异位症（EMs）主要因子宫内膜碎屑返流至盆腹腔所致，异常盆腹腔免疫微环境是异位子宫内膜不能被有效清除的关键因素。本课题以异位灶微环境趋化因子调节环路为核心，以子宫内膜间质细胞（ESC）与单核巨噬细胞(M?)间交叉对话为基本思路，通过建立ESC和M?单独、直接共培养体系，研究内（雌激素）、外（TCDD）环境因素通过趋化因子调节M?的功能，诱导异位灶耐受型M?形成的分子机制，以及耐受型M?进一步诱导na?ve T细胞向Th2型细胞分化，促进病灶局部Th2型免疫优势形成，从而产生针对子宫内膜碎屑自身抗原的免疫耐受，导致异位种植及存活的分子机制。通过建立EMs动物模型，基因沉默和或过表达本课题组发现的关键致病功能基因，及通过过继转输免疫细胞以重建免疫力，体内研究异位灶耐受型M?的形成及其介导病灶局部Th2型免疫优势的分子机制，以解析异位灶耐受型M?在EMs发生与发展中的致病机制。

Endometriosis results from the retrograde menstruation into the pelvis which occurs in almost all menstrual cycles,and the abnormal abdominal immune microenvironment is the key factor that the ectopic tissue can not be effectively cleared.The chemokine network in the milieu is seen as the major mediator for the crosstalking between the endometrium stromal cells(ESC) and macrophage in the present application. In this project,to establish ESC and macrophage co-culture units,we will investigate how the combination of estrogen in the body with the environmental contaminants TCDD regulates the functions of macrophage throuth influencing the chemokine network, and the mechanisms in the formation of tolerant macrophage and which induce Th2-type cells differentiation from na?ve T cells that formes a Th2-type bias in the ectopic milieu.The crosstalking between these cells induce immunotolerance of immunocytes to the retrograde endometrial self-antigens. Thereafter, animal model of endometriosis is used to investigate in vivo the mechanisms of tolerant macrophage formation that induces the Th2-type bias in the ectopic immunotolerant milieu, which contributes to the pathogenesis of endometriosis.