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Cell Mol Immunol. 2016 Jul;13(4):462-73. doi: 10.1038/cmi.2015.22. Epub 2015 Apr 6.

An imbalance between innate and adaptive immune cells at the maternal-fetal interface occurs prior to endotoxin-induced preterm birth.

Author information

1
Department of Obstetrics & Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA.
2
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA.
3
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA.
4
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA.
5
Department of Molecular Obstetrics and Genetics, Wayne State University, Detroit, Michigan, USA.
6
Department of Immunology & Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA.

Abstract

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide. A transition from an anti-inflammatory state to a pro-inflammatory state in the mother and at the maternal-fetal interface has been implicated in the pathophysiology of microbial-induced preterm labor. However, it is unclear which immune cells mediate this transition. We hypothesized that an imbalance between innate and adaptive immune cells at the maternal-fetal interface will occur prior to microbial-induced preterm labor. Using an established murine model of endotoxin-induced PTB, our results demonstrate that prior to delivery there is a reduction of CD4+ regulatory T cells (Tregs) in the uterine tissues. This reduction is neither linked to a diminished number of Tregs in the spleen, nor to an impaired production of IL10, CCL17, or CCL22 by the uterine tissues. Endotoxin administration to pregnant mice does not alter effector CD4+ T cells at the maternal-fetal interface. However, it causes an imbalance between Tregs (CD4+ and CD8+), effector CD8+ T cells, and Th17 cells in the spleen. In addition, endotoxin administration to pregnant mice leads to an excessive production of CCL2, CCL3, CCL17, and CCL22 by the uterine tissues as well as abundant neutrophils. This imbalance in the uterine microenvironment is accompanied by scarce APC-like cells such as macrophages and MHC II+ neutrophils. Collectively, these results demonstrate that endotoxin administration to pregnant mice causes an imbalance between innate and adaptive immune cells at the maternal-fetal interface.

PMID:
25849119
PMCID:
PMC4947814
DOI:
10.1038/cmi.2015.22
[Indexed for MEDLINE]
Free PMC Article

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