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Cited by 332

The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.

Human Placenta Expresses and Secretes NKG2D Ligands via Exosomes that Down-Modulate the Cognate Receptor Expression: Evidence for Immunosuppressive Function

Open access
Hedlund, Malin, Stenqvist, Ann-Christin, Nagaeva, Olga, Kjellberg, Lennart, Wulff, Marianne, Baranov, Vladimir, Mincheva-Nilsson, Lucia·2009·The Journal of Immunology
DOI 10.4049/jimmunol.0803477
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Abstract

During mammalian pregnancy maternal-fetal tolerance involves a number of immunosuppressive factors produced by placenta. Recently, placenta-derived exosomes have emerged as new immune regulators in the maternal immune tolerance. Exosomes are membrane nanovesicles with defined morphology, which are secreted from endosomal multivesicular bodies (MVB) upon fusion with the plasma membrane. Previously, we reported that the MHC class I chain-related (MIC) proteins A and B, human ligands of the activating NK cell receptor NKG2D, are expressed by placenta, sorted to MVB of syncytiotrophoblast and probably released via MIC-bearing exosomes. In this report, we show that the second family of human NKG2D ligands, the UL-16 binding proteins (ULBP), is also expressed by placenta. Importantly, this expression was not due to placental CMV infection. Immunoelectron microscopy disclosed that ULBP1–5 are produced and retained in MVB of the syncytiotrophoblast on microvesicles/exosomes. Using human placenta explant cultures and different assays, we demonstrate that exosomes bearing NKG2D ligands are released by human placenta. Isolated placental exosomes carried ULBP1–5 and MIC on their surface and induced down-regulation of the NKG2D receptor on NK, CD8+, and γδ T cells, leading to reduction of their in vitro cytotoxicity without affecting the perforin-mediated lytic pathway. Release of placental NKG2D ligands via exosomes is an alternative mechanism for generation of bioactive soluble form of these ligands. These findings highlight a role for NKG2D ligand-bearing placental exosomes in the fetal immune escape and support the view of placenta as a unique immunosuppressive organ.

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Metadata

Authors
Hedlund, M., Stenqvist, A.-C., Nagaeva, O., Kjellberg, L., Wulff, M., Baranov, V., & Mincheva-Nilsson, L.
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2009-07-01
Volume
183
Issue
1
Pages
340-351
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.0803477
OpenAlex
W1761567378
Cited by
332
References
53
FWCI
7.26
Type
journal article
Language
en
Open access
bronze

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