1. Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2
- Author
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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], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,immunology [Dendritic Cells] ,T-Lymphocytes ,T-Lymphocytes, Regulatory ,immunology [T-Lymphocytes] ,Immune tolerance ,0302 clinical medicine ,metabolism [Arginase] ,Cell Movement ,Receptor ,enzymology [Fetus] ,Multidisciplinary ,Toll-Like Receptors ,cytology [Fetus] ,medicine.anatomical_structure ,cytology [T-Lymphocytes, Regulatory] ,Cytokines ,ddc:500 ,cytology [Lymph Nodes] ,immunology [T-Lymphocytes, Regulatory] ,Adult ,cytology [T-Lymphocytes] ,T cell ,arginase II, human ,Article ,03 medical and health sciences ,Immune system ,Fetus ,Antigen ,Immunity ,medicine ,Immune Tolerance ,Humans ,immunology [Lymph Nodes] ,Cell Proliferation ,enzymology [Dendritic Cells] ,Arginase ,biosynthesis [Cytokines] ,immunology [Fetus] ,Dendrites ,Dendritic Cells ,030104 developmental biology ,immunology [Toll-Like Receptors] ,immunology [Cytokines] ,Immunology ,Lymph Nodes ,Homeostasis ,030215 immunology - 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.
- Published
- 2018
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