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

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.

Pediatric tolerogenic DCs expressing CD4 and immunoglobulin‐like transcript receptor (ILT)‐4 secrete IL‐10 in response to Fc and adenosine

“…We also show that tmDCs express higher levels of the immunosuppressive A 2A R than classical mDCs. Pediatric tmDCs are phenotypically different than recently described tolerogenic fetal cDC2 cells but appear to be functionally similar, as fetal cDC2 cells suppress ariginase‐2 that is induced by cAMP .…”

Human dendritic cell subsets: an update

“…Fluorescence flow cytometry is the most commonly used platform for identifying human DC. [2][3][4] This has been expanded from the analysis of blood, to single-cell suspensions of tissues including skin, [11][12][13] lung [14][15][16] intestine 17 and liver of humans 2,18,19 and to lymphoid tissue 3,4,[20][21][22] fetal tissues 23 and other body fluids. 24 The Tenth Human Leucocyte Differentiation Antigen workshop has recently reported a range of new antibodies characterized on human DC populations (Table 1).…”

Challenges and emergent solutions for LC‐MS/MS based untargeted metabolomics in diseases

“…Several reasons, however, suggest that metabolomics will continue to find success in enhancing our knowledge of metabolite function, or reveal the impact of metabolite changes on biology and diseases. First, there has been a revisit of basic metabolism and its impact on immunity, and immunometabolomics is an burgeoning field . It has been noted that regulators associated with immunity such mTOR complexes could sense amino acids, and promote cell growth, and T‐cell and monocyte differentiation.…”

“…First, there has been a revisit of basic metabolism and its impact on immunity, and immunometabolomics is an burgeoning field. 139,166 It has been noted that regulators associated with immunity such mTOR complexes could sense amino acids, and promote cell growth, and T-cell and monocyte differentiation. Metabolic pathways such as pentose phosphate, and tricarboxylic acid pathways affect the acquisition of antimicrobial, or inflammatory phenotypes.…”