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The reason for the high percentage of peritoneal T<jats:sub>reg<\/jats:sub> in endometriosis patients is unknown. Here, we show that the proportion of peritoneal T<jats:sub>reg<\/jats:sub> cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of T<jats:sub>reg<\/jats:sub> cells, mainly IL-10<jats:sup>+<\/jats:sup> T<jats:sub>reg<\/jats:sub> cells, decreased. Therefore, 1-MT-pretreated ESCs-educated T<jats:sub>reg<\/jats:sub> cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of T<jats:sub>reg<\/jats:sub> cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for T<jats:sub>reg<\/jats:sub> differentiation in the ectopic lesion, especially that for CD4<jats:sup>high<\/jats:sup> T<jats:sub>reg<\/jats:sub>. Therefore, MRC2-silenced ESCs-educated T<jats:sub>reg<\/jats:sub> manifested a stronger suppressive function <jats:italic>in vitro<\/jats:italic>. Consistently, the percentage of T<jats:sub>reg<\/jats:sub> increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions <jats:italic>in vivo<\/jats:italic>. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of T<jats:sub>reg<\/jats:sub> and is involved in the development of endometriosis. Thus, blockage of IDO1 in the ectopic lesion, which does not influence physiological functions of estrogen, may be considered a potential therapy for endometriosis.<\/jats:p>","DOI":"10.1038\/cddis.2016.375","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T13:47:52Z","timestamp":1480600072000},"page":"e2489-e2489","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis"],"prefix":"10.1038","volume":"7","author":[{"given":"Chunyan","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dajin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,1]]},"reference":[{"key":"BFcddis2016375_CR1","first-page":"19","volume-title":"Endometriosis: Epidemiology, and Etiological Factors","author":"LC Giudice","year":"2012","unstructured":"Giudice LC, Evers JLH, Healy DL. 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