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Prevention of CpG-induced pregnancy disruption by adoptive transfer of in vitro-induced regulatory T cells.

AbstractOBJECTIVE:
To elucidate the mechanism by which embryo-resorption and preterm birth were enhanced by pathogenic CpG motif and to develop a counter strategy for normal pregnancy outcome.
METHODS:
This is an animal model-based study. In pregnant nonobese diabetic (NOD) mice and wild-type (WT) mice in the same strain background, an infection was mimicked by toll-like receptor 9 (TLR9) activation through CpG1826-injection. In vivo inactivation of IL-10 was performed to enhance pregnancy loss. Regulatory T cells induced by FTY720 in vitro from splenic CD4+CD25-Foxp3- cells (iTreg cells) were transferred to improve pregnancy outcomes in NOD mice.
RESULTS:
Embryo-resorption and preterm birth were readily induced by CpG1826 in NOD mice, but not in WT mice. However, inactivation of IL-10 using neutralizing antibody injections enhanced pregnancy loss in WT mice exposed to CpG, while adoptive transfer of iTreg cells increased decidual Foxp3+ Treg cells and IL-10+ cell number and rescued pregnancy.
CONCLUSIONS:
NOD mice are prone to abortion and preterm birth. This can be attributed to lacking Treg cells and insufficient IL-10 expression. Adoptive transfer of iTreg cells can rescue CpG-mediated pregnancy failure.
AuthorsYi Lin, Xiaorui Liu, Bin Shan, Ji Wu, Surendra Sharma, Yun Sun
JournalPloS one (PLoS One) Vol. 9 Issue 4 Pg. e94702 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24714634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Oligodeoxyribonucleotides
  • Interleukin-10
Topics
  • Abortion, Spontaneous (chemically induced, immunology, prevention & control)
  • Adoptive Transfer
  • Animals
  • Disease Models, Animal
  • Female
  • Forkhead Transcription Factors (metabolism)
  • Immunophenotyping
  • Interleukin-10 (metabolism)
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred NOD
  • Oligodeoxyribonucleotides (administration & dosage, adverse effects)
  • Phenotype
  • Pregnancy
  • Pregnancy Outcome
  • Premature Birth (chemically induced, immunology, prevention & control)
  • T-Lymphocytes, Regulatory (immunology, metabolism)

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