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Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2

Authors :
Yie Hou Lee
Donovan Low
Yiping Fan
Nurhidaya Binte Shadan
Edwin Huang Kunxiang
Venetia Bigley
Sandra Hubert
Dedrick Kok Hong Chan
Matthew Collin
Anis Larbi
Gillian Low
John Kit Chung Tam
Peter See
Michael Poidinger
Erin Soon
Kaibo Duan
Citra Nurfarah Zaini Mattar
Mahesh Choolani
Esther Wing Hei Mok
Muzlifah Haniffa
Salvatore Albani
Christopher Schuster
Jerry Kok Yen Chan
Baptiste Janela
Naomi McGovern
Florent Ginhoux
Xiao-Nong Wang
Tony Kiat Hon Lim
Evan W. Newell
Rasha Msallam
Leong Jing Yao
Adelheid Elbe-Bürger
Josephine Lum
Ivy Low
Hermi Sumatoh
Andreas Schlitzer
Amanda Shin
Ker-Kan Tan
McGovern, Naomi [0000-0001-5200-2698]
Apollo - University of Cambridge Repository
Source :
Nature 546(7660), 662-666 (2017). doi:10.1038/nature22795
Publication Year :
2018
Publisher :
Springer Science and Business Media LLC, 2018.

Abstract

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

Details

Database :
OpenAIRE
Journal :
Nature <London> 546(7660), 662-666 (2017). doi:10.1038/nature22795
Accession number :
edsair.doi.dedup.....3a347f7b3181da6dfcbf55538f27f7b2
Full Text :
https://doi.org/10.17863/cam.24447