Reproductive outcomes after pregnancy-induced displacement of preexisting microchimeric cells

• 成果类型: Article
• 署名作者: Shao, Tzu-Yu; Kinder, Jeremy M.; Harper, Gavin; Pham, Giang; Peng, Yanyan; Liu, James; Gregory, Emily J.; Sherman, Bryan E.; Wu, Yuehong; Iten, Alexandra E.; Hu, Yueh-Chiang; Russi, Abigail E.; Erickson, John J.; Miller-Handley, Hilary; Way, Sing Sing
• 署名单位: University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9251
• DOI: 10.1126/science.adf9325
• 发表日期: 2023-09-22
• 页码: 1324-1330
• 关键词: regulatory t-cells; leishmania-major; risk-factor; fetal; foxp3(+); tolerance; paternity; memory; preeclampsia; persistence

摘要

Pregnancy confers partner-specific protection against complications in future pregnancy that parallel persistence of fetal microchimeric cells (FMcs) in mothers after parturition. We show that preexisting FMcs become displaced by new FMcs during pregnancy and that FMc tonic stimulation is essential for expansion of protective fetal-specific forkhead box P3 (FOXP3)-positive regulatory T cells (T-reg cells). Maternal microchimeric cells and accumulation of T-reg cells with noninherited maternal antigen (NIMA) specificity are similarly overturned in daughters after pregnancy, highlighting a fixed microchimeric cell niche. Whereas NIMA-specific tolerance is functionally erased by pregnancy, partner-specific resiliency against pregnancy complications persists in mothers despite paternity changes in intervening pregnancy. Persistent fetal tolerance reflects FOXP3 expression plasticity, which allows mothers to more durably remember their babies, whereas daughters forget their mothers with new pregnancy-imprinted immunological memories.