Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6
Open accessAbstract
Fetal loss in animals and humans is frequently associated with inflammatory conditions. D6 is a promiscuous chemokine receptor with decoy function, expressed in lymphatic endothelium, that recognizes and targets to degradation most inflammatory CC chemokines. Here, we report that D6 is expressed in placenta on invading extravillous trophoblasts and on the apical side of syncytiotrophoblast cells, at the very interface between maternal blood and fetus. Exposure of D6 −/− pregnant mice to LPS or antiphospholipid autoantibodies results in higher levels of inflammatory CC chemokines and increased leukocyte infiltrate in placenta, causing an increased rate of fetal loss, which is prevented by blocking inflammatory chemokines. Thus, the promiscuous decoy receptor for inflammatory CC chemokines D6 plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies.
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The neutralizing antibodies for CCL2 and CCL3/4/5 have been shown to be effective in neutralizing the corresponding chemokines in published experiments.
“These antibodies have been shown to be effective in neutralizing the corresponding chemokines in published experiments (Martinez de la Torre et al., 2007; Pace et al., 2012).”
From p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells (2013) · cites this paper as Martinez de la Torre et al., 2007
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- Authors
- Martinez de la Torre, Y., Buracchi, C., Borroni, E. M., Dupor, J., Bonecchi, R., Nebuloni, M., Pasqualini, F., Doni, A., Lauri, E., Agostinis, C., Bulla, R., Cook, D. N., Haribabu, B., Meroni, P., Rukavina, D., Vago, L., Tedesco, F., Vecchi, A., Lira, S. A., Locati, M., & Mantovani, A.
- Affiliations
- *Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano, 20089 Milan, Italy;
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- University of Milan (IT)
- University of Trieste (IT)
- Duke University (US)
- University of Louisville (US)
- **Allergy, Clinical Immunology, and Rheumatology Unit, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Milan, 21049 Milan, Italy;
- University of Rijeka (HR)
- Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029
- Corresponding author
- Mantovani, Alberto
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-02-13
- Volume
- 104
- Issue
- 7
- Pages
- 2319-2324
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1892950
- OpenAlex
- W2015456374
- Cited by
- 178
- References
- 34
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 8 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 13 · 2015: 3 · 2014: 11 · 2013: 14 · 2012: 9
- FWCI
- 8.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- decoy receptor, fetal death, miscarriage, placenta, extravillous trophoblast, syncytiotrophoblast, CC chemokines, inflammation, lipopolysaccharide, antiphospholipid antibodies, autoantibodies, leukocyte infiltration, maternal-fetal interface, pregnancy
- MeSH terms
- Chemokine Receptor D6, Animals, Female, Fetal Death, Inflammation, Leukocytes, Lipopolysaccharides, Placenta, Pregnancy, Trophoblasts, Antibodies, Antiphospholipid, Mice, Knockout, Receptors, Chemokine, Chemokines, CC, Mice, Receptors, CCR10
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