Affiliation:
1. The CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical Sciences Division of Life Sciences and Medicine University of Science and Technology of China Hefei China
2. Institute of Immunology University of Science and Technology of China Hefei China
Abstract
AbstractProblemImpairment of PBX1 expression in decidual natural killer (dNK) cells is associated with the pathogenesis of unexplained recurrent spontaneous abortion, which results in fetal growth restriction (FGR) by affecting the secretion of downstream growth factors. However, whether other mechanisms limit embryo growth in decidua containing PBX1‐deficient natural killer (NK) cells is unknown.Method of studyPbx1f/f; Ncr1Cre mice were employed to explore the underlying mechanisms by which PBX1− NK cells affect embryonic development. To simulate the clinical testing of pregnant women, Doppler ultrasound imaging was used to detect embryo implantation and development. Differentially expressed genes (DEGs) in PBX1− NK cells that may affect normal pregnancy were screened using RNA‐sequencing and real‐time PCR. Immune cell changes caused by DEGs were detected by flow cytometry. Finally, the mechanism of FGR was explored by injecting the protein LCN2, corresponding to the selected DEG, into mice.ResultsWe verified the embryonic dysplasia in pregnant Pbx1f/f; Ncr1Cre mice by Doppler ultrasound imaging and found that LCN2 was upregulated in dNK cells. We also observed higher infiltration of neutrophils and macrophages in the decidua of Pbx1f/f; Ncr1Cre mice. Finally, we found an increase in the number and activation of neutrophils at the maternal‐fetal interface after injecting LCN2 into pregnant mice and observed that these mice showed signs of FGR.ConclusionExcessive LCN2 secreted by PBX1− dNK cells at the maternal‐fetal interface recruit neutrophils and causes an inflammatory response, which is related to FGR.
Funder
National Natural Science Foundation of China
Subject
Obstetrics and Gynecology,Reproductive Medicine,Immunology,Immunology and Allergy,Obstetrics and Gynecology,Immunology
Cited by
2 articles.
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