脱落性自然杀手细胞的功能障碍是由dMDSCs的IDO下调引起的,dMDSCs具有Toxoplasma gondii感染
Yu Wang1, Xiaoyue Zhao2, Zhidan Li1
1Department of Immunology, Binzhou Medical University, Yantai, 264003, Shandong, PR China.
Communications biology
|May 31, 2024
概括
托克索普拉斯马淋巴菌感染通过降低髓质衍生抑制细胞 (MDSCs) 中的胺2,3-二氧化酶 (IDO) 的作用来破坏母胎耐受性. 这导致了不良的妊娠结果,突出了一个新的分子机制.
科学领域:
- 免疫学 免疫学 免疫学
- 生殖生物学 生殖生物学
- 寄生虫学的寄生虫学
背景情况:
- 骨髓系衍生抑制细胞 (MDSCs) 对于母胎耐受性至关重要,部分通过二二氧化酶 (IDO).
- 毒素菌 (T. gondii) 感染可能会损害母胎免疫环境,导致不良妊娠结果.
- 淋巴菌对果叶MDSCs (dMDSCs) 中的IDO表达的影响及其潜在机制在很大程度上是未知的.
研究的目的:
- 研究T. gondii感染如何影响dMDSC中的IDO表达.
- 阐明T. gondii影响IDO表达和影响怀孕结果的分子机制.
- 探索IDO在T. gondii诱导的不良妊娠结果中的作用.
主要方法:
- 在T. gondii感染的dMDSC中分析IDOmRNA和蛋白质水平.
- 对调节IDO表达的信号通路 (STAT3/p52-RelB,SOCS3) 的研究.
- 使用IDO淘汰和野生型小鼠进行体内研究,评估怀孕结果和kynurenine的治疗效果.
- 检查Kynurenine/AhR/SP1通路及其对TGF-β,IL-10和dNK细胞功能的影响.
主要成果:
- 淋巴球菌感染增加了IDO mRNA,但在dMDSC中降低了IDO蛋白水平.
- IDO上调是由STAT3/p52-RelB途径调节的,而蛋白质水平的降低则是由SOCS3诱导的降解引起的.
- IDO缺乏症加剧了感染小鼠的不良怀孕结果,这些结果通过金氨酸治疗得到改善.
- 由于T. gondii诱导的dMDSC IDO的减少,dNK细胞通过Kyn/AhR/SP1通路降低了TGF-β和IL-10,导致dNK细胞功能障碍和不良妊娠结果.
结论:
- 淋巴菌感染通过不同的转录和后转录机制在dMDSC中失调IDO表达.
- IDO在缓解T. gondii诱导的不良妊娠结果方面发挥着保护作用.
- 这项研究揭示了一种新的分子途径,将T. gondii感染,IDO减少,dNK细胞功能障碍和不良妊娠结果联系起来.
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