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Am J Reprod Immunol. 2015 Jun;73(6):522-35. doi: 10.1111/aji.12364. Epub 2015 Jan 30.

Maternal Lipopolysaccharide Exposure Promotes Immunological Functional Changes in Adult Offspring CD4+ T Cells.

Author information

1
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
2
Caner Research Center, Shandong University, Jinan, Shandong, China.
3
Periodical Department, Binzhou Medical University, Yantai, Shandong, China.
4
Department of Zoology and Developmental Biology, College of Life Sciences, Nankai University, Tianjin, China.
5
Biomedical Translational Research Institute, International Immunology Center, Jinan University, Guangzhou, China.

Abstract

PROBLEM:

Maternal immune activation (MIA) is a risk factor for autism and schizophrenia. However, how MIA affects offspring immune function remains unknown.

METHOD OF STUDY:

To investigate the effect of MIA on the offspring, pregnant C57BL/6J mice were given an intraperitoneal injection of 50 μg/kg lipopolysaccharide (LPS) on gestational day 12.5.

RESULTS:

Adult LPS-treated offspring were hyper-reactive to LPS, and enhanced tumor necrosis factor-α production was observed. CD4+ T cells from LPS offspring had an elevated percentage of interferon (IFN)-γ(+) CD4+ T cells and interleukin (IL)-17A+ CD4+ T cells in the spleen, IL-17A+ CD4+ T cells in the liver, and CD4+ Foxp3+ T cells in the spleen. LPS offspring CD4+ T cells showed increased proliferation and an enhanced survival rate. DNA microarray analysis of resting LPS offspring CD4+ T cells identified eight up-regulated genes, most of which encoded transcription factors. Quantitative liquid chromatography-mass spectrometry identified 18 up-regulated proteins in resting LPS offspring CD4+ T cells and five up-regulated proteins in activated LPS offspring CD4+ T cells, most of which participated in the PANTHER Gene Ontology metabolic process.

CONCLUSIONS:

Our results showed that MIA to LPS up-regulated proteins involved in metabolic process in CD4+ T cells from LPS offspring that might contribute to the hyperactivated immune response of adult LPS offspring.

KEYWORDS:

CD4+ T cells study; lipopolysaccharide; maternal immune activation; mouse model; offspring immune response

PMID:
25640465
DOI:
10.1111/aji.12364
[Indexed for MEDLINE]

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