title: Excessive TLR9 signaling contributes to the pathogenesis of spontaneous abortion through impairment of Treg cell survival by activation of Caspase 8/3.
abstract: BACKGROUND
  The pregnant uterine microenvironment is repleted with Toll-like receptors (TLRs), however, their roles of these receptors in establishing tolerance to growing fetus are largely unknown.
  
  
  RESULTS
  Decidual TLR1, TLR3, TLR4, TLR8 and TLR9 gene expressions were significantly over-expressed in patients of spontaneous abortion compared with elective abortion with normal pregnancy. In particular, the expression of TLR4 and TLR9 mRNA was considerably higher than that of remaining TLRs. We mimic TLR9 signal with combination of its pathogenic ligand CpG ODN and antagonists ODN in a well-established abortion-prone CBA/J×DBA/2 model. CpG ODN dramatically boosted fetal loss and lowered the proportion of Regulatory cells (Treg cells) in vivo. CpG ODN directly triggered the impaired survival and increased activity of Caspase 8/3 of Treg cells in vitro. These effects were blocked by antagonist ODN.
  
  
  CONCLUSIONS
  Excessive TLR9 signaling contributed to maternal-fetal tolerance disruption via an effect on Treg cell survival by activation of Caspase 8/3.
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Kang
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Zhilan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Tongfei
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China. Electronic address: zamzkh0526@126.com.
authors.forename: Aimin
authors.initials: A
authors.lastname: Zhao
mesh_terms: D000022:Abortion, Spontaneous / Q000503:physiopathology*; D000328:Adult; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics; D050378:T-Lymphocytes, Regulatory; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis* / Q000235:genetics; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C495345:TLR4 protein, human; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8
keywords: Caspase 3; Caspase 8; Regulatory T cells; Spontaneous abortion; Survival; Toll like receptor 9