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 accessAbstract
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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Cites
1 retracted
Pregnancy-Associated Exosomes and Their Modulation of T Cell Signaling
Taylor, D. D., Akyol, S., & Gercel-Taylor, C. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.3.1534 · Cited by 297
RetractedExosomes: composition, biogenesis and function
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The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor
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Costimulation of CD8αβ T cells by NKG2D via engagement by MIC induced on virus-infected cells
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Exosomes: A Common Pathway for a Specialized Function
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Iraci, N., Leonardi, T., Gessler, F., Vega, B., & Pluchino, S. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020171 · Cited by 301
NKG2D: A Master Regulator of Immune Cell Responsiveness
Wensveen, F. M., Jelenčić, V., & Polić, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00441 · Cited by 271
Harnessing the exosome-induced immune response for cancer immunotherapy
Gehrmann, U., Näslund, T. I., Hiltbrunner, S., Larssen, P., & Gabrielsson, S. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.05.003 · Cited by 111
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
- OpenAlex
- W1761567378
- Cited by
- 332
- References
- 53
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Human Placenta Expresses and Secretes NKG2D Ligands via Exosomes that Down-Modulate the Cognate Receptor Expression: Evidence for Immunosuppressive Function. https://app.cochat.ai/papers/10.4049/jimmunol.0803477
- The paper
- Hedlund, M., Stenqvist, A.-C., Nagaeva, O., Kjellberg, L., Wulff, M., Baranov, V., & Mincheva-Nilsson, L. (2009). Human Placenta Expresses and Secretes NKG2D Ligands via Exosomes that Down-Modulate the Cognate Receptor Expression: Evidence for Immunosuppressive Function. The Journal of Immunology. https://doi.org/10.4049/jimmunol.0803477
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
