Evidence map›Paper›PMID 40401522›Full record

ArticleJCI insight2025

Fetoplacental extracellular vesicles deliver conceptus-derived antigens to maternal secondary lymphoid tissues for immune recognition.

Juliana S Powell, Adriana T Larregina, William J Shufesky, Mara Lg Sullivan, Donna Beer Stolz, Stephen J Gould, Geoffrey Camirand, Sergio D Catz, Simon C Watkins, Yoel Sadovsky and 1 more

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Juliana S PowellT.E. Starzl Transplantation Institute, Department of Surgery.
Adriana T LarreginaDepartment of Dermatology.
William J ShufeskyT.E. Starzl Transplantation Institute, Department of Surgery.
Mara Lg SullivanDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Donna Beer StolzDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Stephen J GouldDepartment of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Geoffrey CamirandT.E. Starzl Transplantation Institute, Department of Surgery.
Sergio D CatzThe Scripps Research Institute, La Jolla, California, USA.
Simon C WatkinsDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Yoel SadovskyDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute.
Adrian E MorelliT.E. Starzl Transplantation Institute, Department of Surgery.

Funding

Interdisciplinary Training in Transplantation BiologyT32AI074490 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Angus W Thomson · 2007 to 2026
$4.2M
Graft extracellular vesicles as promoters of anti-donor immunity in cardiac and skin transplantationR01AI174273 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MORELLI, ADRIAN E. · 2022 to 2025
$3.3M
Role of neurokinin 1 receptor signaling in keratinocytes in allergic contact dermatitisR01AI168142 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LARREGINA, ADRIANA T, MORELLI, ADRIAN E. · 2022 to 2025
$3.0M
Placental extracellular vesicles as regulators of maternal adaptive immunityR01AI148690 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MORELLI, ADRIAN E., SADOVSKY, YOEL · 2019 to 2023
$2.7M
Bigfoot Spectral Cell SorterS10OD032265 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KANE, LAWRENCE P. · 2022 to 2022
$755k
NIAID NIH HHS R01 AI148690NIAID NIH HHS R01 AI168142NIAID NIH HHS R01 AI174273NIAID NIH HHS T32 AI074490NIH HHS S10 OD032265
6 · The paper itself

Abstract

Pregnancy is an immunological paradox where despite a competent maternal immune system, regulatory mechanisms at the fetoplacental interface and maternal secondary lymphoid tissues (SLTs) circumvent rejection of semi-allogeneic concepti. Small extracellular vesicles (sEVs) are a vehicle for intercellular communication; nevertheless, the role of fetoplacental sEVs in transport of antigens to maternal SLTs has not been conclusively demonstrated. Using mice in which the conceptus generates fluoroprobe-tagged sEVs shed by the plasma membrane or released from the endocytic compartment, we show that fetoplacental sEVs are delivered to immune cells in the maternal spleen. Injection of sEVs from placentas of females impregnated with Act-mOVA B6 males elicited suboptimal activation of OVA-specific CD8+ OT-I T cells in virgin females as occurs during pregnancy. Furthermore, when OVA+ concepti were deficient in Rab27a, a protein required for sEV secretion, OT-I cell proliferation in the maternal spleen was decreased. Proteomics analysis revealed that mouse trophoblast sEVs were enriched in antiinflammatory and immunosuppressive mediators. Translational relevance was tested in humanized mice injected using sEVs from cultures of human trophoblasts. Our findings show that sEVs deliver fetoplacental antigens to the mother's SLTs that are recognized by maternal T cells. Alterations of such a mechanism may lead to pregnancy disorders.

Indexed as

AntigensExtracellular VesiclesLymphoid TissuePlacentaAnimalsFemaleHumansMaleMaternal-Fetal ExchangeMiceMice, Inbred C57BLPregnancyrab GTP-Binding ProteinsSpleenTrophoblastsAntigensrab GTP-Binding ProteinsAntigenImmunologyMouse modelsReproductive biologyT cells

Identifiers

PMID40401522
PMCPMC12128977

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.