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

Lookup NU author(s): Dr Naomi McGovern, Dr Xiao Wang, Dr Venetia Bigley, Professor Matthew Collin, Professor Muzlifah Haniffa

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2017.

For re-use rights please refer to the publisher's terms and conditions.


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.


Publication metadata

Author(s): McGovern N, Shin A, Low G, Low D, Duan K, Yao LJ, Msallam R, Low I, Shadan NB, Sumatoh HR, Soon E, Lum J, Mok E, Hubert S, See P, Kunxiang EH, Lee YH, Janela B, Choolani M, Mattar CNZ, Fan Y, Lim TKH, Hong DK, Tan KK, Tam JKC, Schuster C, Elbe-Bürger A, Wang XN, Bigley V, Collin M, Haniffa M, Schlitzer A, Poidinger M, Albani S, Larbi A, Newell EW, Chan JKY, Ginhoux F

Publication type: Article

Publication status: Published

Journal: Nature

Year: 2017

Volume: 546

Pages: 662-666

Print publication date: 29/06/2017

Online publication date: 14/06/2017

Acceptance date: 27/04/2017

Date deposited: 21/06/2017

ISSN (print): 0028-0836

ISSN (electronic): 1476-4687

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/nature22795

DOI: 10.1038/nature22795

PubMed id: 28614294


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