title: CD4+Foxp3+ regulatory T cell differentiation mediated by endometrial stromal cell-derived TECK promotes the growth and invasion of endometriotic lesions.
abstract: Endometriosis is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissue. The proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) is significantly increased in the peritoneal fluid of women with endometriosis. The thymus-expressed chemokine TECK/CCL25 directly promotes the invasiveness of endometrial stromal cells (ESCs). The aim of this study was to investigate the effects of ESC-derived TECK on the crosstalk between Tregs and ESCs in the progress of endometriosis. We determined that the percentage of Tregs and the concentration of TECK increased in the peritoneal fluid with the progression of endometriosis. The supernatant from co-cultured human ESCs and macrophages not only induced Treg differentiation and increased Treg expression of interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and CD73 by activating the AKT/STAT3 signaling pathway but also repressed Treg apoptosis by downregulating Fas and FasL expression and enhanced the Treg-mediated suppression of CD4(+)CD25(-) T cells. In addition, in vitro and in vivo trials confirmed that these effects could be inhibited by anti-TECK neutralizing Abs. The secretion of IL-10 and TGF-β by Tregs increased MMP2 expression and decreased TIMP1 expression and further stimulated the proliferation and invasion of ESCs and the growth of ectopic lesions. These results indicate that TECK derived from ESCs and macrophages upregulates the number and function of Tregs in the ectopic milieu, which contributes to endometriotic immunotolerance and high levels of ESC proliferation and invasion, thereby facilitating the progression of endometriosis.
authors.affiliation: 1] Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China [2] Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
authors.forename: M-Q
authors.initials: MQ
authors.lastname: Li
authors.affiliation: 1] Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China [2] Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: K-K
authors.initials: KK
authors.lastname: Chang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Meng
authors.affiliation: 1] Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China [2] Department of Obstetrics and Gynecology, The Fourth Hospital of Soochow University, WuXi, China.
authors.forename: L-B
authors.initials: LB
authors.lastname: Liu
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Mei
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China [2] Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: 1] Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China [2] Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
authors.forename: L-P
authors.initials: LP
authors.lastname: Jin
authors.affiliation: 1] Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China [2] Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
authors.forename: D-J
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D004715:Endometriosis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D004717:Endometrium / Q000166:cytology / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: C108074:CCL25 protein, human; D015704:CD4 Antigens; D019742:Chemokines, CC; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10