Luan Rong, Cheng Hao, Li Lin, Zhao Qiang, Liu Hui, Wu Zhenzhou, Zhao Liqing, Yang Jinghua, Hao Jianlei, Yin Zhinan
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Caner Research Center, Shandong University, Jinan, Shandong, China.
Am J Reprod Immunol. 2015 Jun;73(6):522-35. doi: 10.1111/aji.12364. Epub 2015 Jan 30.
Maternal immune activation (MIA) is a risk factor for autism and schizophrenia. However, how MIA affects offspring immune function remains unknown.
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.
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.
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.
母体免疫激活（MIA）是自闭症和精神分裂症的一个风险因素。然而，MIA如何影响后代的免疫功能仍不清楚。
为了研究MIA对后代的影响，在妊娠第12.5天给怀孕的C57BL/6J小鼠腹腔注射50μg/kg脂多糖（LPS）。
成年期接受LPS处理的后代对LPS反应过度，且观察到肿瘤坏死因子-α产生增加。来自LPS处理后代的CD4+T细胞在脾脏中干扰素（IFN）-γ(+)CD4+T细胞和白细胞介素（IL）-17A+CD4+T细胞的百分比升高，在肝脏中IL-17A+CD4+T细胞升高，在脾脏中CD4+Foxp3+T细胞升高。LPS处理后代的CD4+T细胞显示增殖增加和存活率提高。对静息状态的LPS处理后代CD4+T细胞进行DNA微阵列分析，鉴定出8个上调基因，其中大多数编码转录因子。定量液相色谱-质谱法鉴定出静息状态的LPS处理后代CD4+T细胞中有18种上调蛋白，激活状态的LPS处理后代CD4+T细胞中有5种上调蛋白，其中大多数参与PANTHER基因本体代谢过程。
我们的结果表明，MIA-LPS上调了LPS处理后代CD4+T细胞中参与代谢过程的蛋白，这可能导致成年期LPS处理后代的免疫反应过度激活。
