title: 17β-Oestradiol enhances the expansion and activation of myeloid-derived suppressor cells via signal transducer and activator of transcription (STAT)-3 signalling in human pregnancy.
abstract: During a successful pregnancy, the maternal immune system plays a critical role in maintaining immunotolerance towards semi-allogeneic fetal antigens. Recent studies have indicated that myeloid-derived suppressor cells (MDSCs) are active players in establishing fetal-maternal tolerance; however, the underlying mechanism remains poorly understood. In this study, we observed a significant expansion of monocytic MDSCs (M-MDSCs) in the peripheral blood of pregnant women, which suppressed T cell responses in a reactive oxygen species-dependent manner and required cell-cell contact. The number of M-MDSCs correlated positively with serum oestrogen and progesterone levels. Administration of 17β-oestradiol, but not progesterone, enhanced both the expansion and suppressive activity of M-MDSCs through signal transducer and activator of transcription (STAT)-3. Pretreatment with STAT-3 inhibitor JSI-124 almost completely abrogated the effects of 17β-oestradiol on MDSCs. Collectively, these results demonstrate that 17β-oestradiol-induced STAT-3 signalling plays an important role in both the expansion and activation of MDSCs during human pregnancy, which may benefit the development of novel therapeutic strategies for prevention of immune-related miscarriage.
authors.affiliation: Program in Immunology, Affiliated Guangzhou Women and Childrens Medical Center, Zhongshan School of Medicine.|Institute of Human Virology, Sun Yat-Sen University, Guangzhou.
authors.forename: T
authors.initials: T
authors.lastname: Pan
authors.affiliation: Institute of Human Virology, Sun Yat-Sen University, Guangzhou.
authors.forename: L
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Chinese Ministry of Education, Guangzhou.
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.affiliation: Institute of Human Virology, Sun Yat-Sen University, Guangzhou.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Institute of Human Virology, Sun Yat-Sen University, Guangzhou.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Chinese Ministry of Education, Guangzhou.
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Chinese Ministry of Education, Guangzhou.
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Chinese Ministry of Education, Guangzhou.
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.affiliation: National-regional Key Technology Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen.
authors.forename: N
authors.initials: N
authors.lastname: Ma
authors.affiliation: National-regional Key Technology Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Sun Yat-Sen University, Guangzhou.|Department of Cell Biology, Southern Medical University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Program in Immunology, Affiliated Guangzhou Women and Childrens Medical Center, Zhongshan School of Medicine.|Institute of Human Virology, Sun Yat-Sen University, Guangzhou.|Department of Cell Biology, Southern Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000328:Adult; D002450:Cell Communication / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood; D005260:Female; D005333:Fetus; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy; D061251:Primary Cell Culture; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D004967:Estrogens; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014315:Triterpenes; D011374:Progesterone; D004958:Estradiol; C038106:cucurbitacin I
keywords: 17β-oestradiol; MDSC; STAT-3; human pregnancy