@article{5f6c7e28365d4b8d8656ec4b805bb0e5,
title = "Regulatory T Cells Play a Role in a Subset of Idiopathic Preterm Labor/Birth and Adverse Neonatal Outcomes",
abstract = "Regulatory T cells (Tregs) have been exhaustively investigated during early pregnancy; however, their role later in gestation is poorly understood. Herein, we report that functional Tregs are reduced at the maternal-fetal interface in a subset of women with idiopathic preterm labor/birth, which is accompanied by a concomitant increase in Tc17 cells. In mice, depletion of functional Tregs during late gestation induces preterm birth and adverse neonatal outcomes, which are rescued by the adoptive transfer of such cells. Treg depletion does not alter obstetrical parameters in the mother, yet it increases susceptibility to endotoxin-induced preterm birth. The mechanisms whereby depletion of Tregs induces adverse perinatal outcomes involve tissue-specific immune responses and mild systemic maternal inflammation, together with dysregulation of developmental and cellular processes in the placenta, in the absence of intra-amniotic inflammation. These findings provide mechanistic evidence supporting a role for Tregs in the pathophysiology of idiopathic preterm labor/birth and adverse neonatal outcomes.",
keywords = "T cells, amniotic fluid, decidua, fetal growth restriction, maternal-fetal interface, myometrium, neonate, parturition, placenta, prematurity",
author = "Nardhy Gomez-Lopez and Marcia Arenas-Hernandez and Roberto Romero and Derek Miller and Valeria Garcia-Flores and Yaozhu Leng and Yi Xu and Jose Galaz and Hassan, {Sonia S.} and Hsu, {Chaur Dong} and Harley Tse and Carmen Sanchez-Torres and Bogdan Done and Tarca, {Adi L.}",
note = "Funding Information: We thank the physicians, nurses, and research assistants from the Center for Advanced Obstetrical Care and Research, Intrapartum Unit, Perinatology Research Branch Clinical Laboratory, and Perinatology Research Branch Perinatal Translational Science Laboratory for help with collecting and processing samples. We also thank Tatjana Milovic, Amapola Balancio, Hong Meng, Gaurav Bhatti, and Rebecca Slutsky for help with carrying out some experiments in mice, data analysis, and/or helpful discussion of the findings. This research was supported in part by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), and in part with federal funds from NICHD/NIH/DHHS under contract HHSN275201300006C. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health. R.R. contributed to this work as part of his official duties as an employee of the U.S. federal government. N.G.-L. conceived, designed, and supervised the study. M.A.-H. D.M. Y.L. V.G.-F. Y.X. and J.G. performed the experiments. N.G.-L. M.A.-H. R.R. B.D. A.L.T. D.M. V.G.-F. Y.L. and Y.X. analyzed the data. R.R. S.S.H. and C.-D.H. provided human samples used in the study and intellectual input. H.T. and C.S.-T. provided intellectual input and helpful discussion of the findings. N.G.-L. M.A.-H. D.M. and R.R. wrote the manuscript. All authors revised and provided feedback for the final version of the manuscript. The authors declare no competing interests. Funding Information: We thank the physicians, nurses, and research assistants from the Center for Advanced Obstetrical Care and Research, Intrapartum Unit, Perinatology Research Branch Clinical Laboratory, and Perinatology Research Branch Perinatal Translational Science Laboratory for help with collecting and processing samples. We also thank Tatjana Milovic, Amapola Balancio, Hong Meng, Gaurav Bhatti, and Rebecca Slutsky for help with carrying out some experiments in mice, data analysis, and/or helpful discussion of the findings. This research was supported in part by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), and in part with federal funds from NICHD/NIH/DHHS under contract HHSN275201300006C . This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health . R.R. contributed to this work as part of his official duties as an employee of the U.S. federal government. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = jul,
day = "7",
doi = "10.1016/j.celrep.2020.107874",
language = "English (US)",
volume = "32",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}