During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells1,2, substances from ingested amniotic fluid3,4, food antigens5, and microbes6. 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.
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Gene Expression Omnibus
This work was supported by Singapore Immunology Network core funding (F.G. and E.W.N.), Biomedical Research Council (BMRC) Young Investigator Grant (N.McG.), Austrian Science Fund (P19474-B13, W1248-B30 to A.E.-B.), BMRC SPF2014/00 (S.A.), and the Singapore Ministry of Health’s National Medical Research Council (J.K.Y.C, CSIRG/1383/2014, CSA(SI)/008/2016/). We thank L. Robinson for manuscript editing.
Extended data figures
Conserved Top Ranked genes CD14+ cells.
Conserved Bottom Ranked genes CD14+ cells.
Conserved Top Ranked genes cDC1 cells.
Conserved Bottom Ranked genes cDC1 cells.
Conserved Top Ranked genes cDC2 cells.
Conserved Bottom Ranked genes cDC2 cells.
Ingenuity Pathway Analysis of fetal and adult CD14+ cells conserved genes.
Ingenuity Pathway Analysis of fetal and adult cDC1 conserved genes.
Ingenuity Pathway Analysis of fetal and adult cDC2 conserved genes.
Z scores for list of DEG between fetal and adult APC.
Expression level of DEG between fetal and adult APC.
Ingenuity Pathway Analysis of DEG between fetal and adult APC.
Antibodies used for flow cytometry and CyTOF.
About this article
Seminars in Immunopathology (2017)