Evidence map›Paper›PMID 37815869›Full record

ArticleJCI insight2023

Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation.

Fang Lyu, Chase Burzynski, Yuan Yuan Fang, Aya Tal, Alice Y Chen, Jacqueline Kisa, Kriti Agrawal, Yuval Kluger, Hugh S Taylor, Reshef Tal

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
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

11 citing papers in PubMed, 11 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Fang LyuDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Chase BurzynskiDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Yuan Yuan FangDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Aya TalDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Alice Y ChenDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Jacqueline KisaDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Kriti AgrawalDepartment of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Yuval KlugerDepartment of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Hugh S TaylorDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Reshef TalDepartment of Obstetrics, Gynecology and Reproductive Sciences, and.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
THE ROLE OF MESENCHYMAL PROGENITOR CELLS IN ABNORMAL UTERINE REPAIRR01HD109326 · NICHD · YALE UNIVERSITY · PI Reshef Tal · 2023 to 2026
$2.4M
NCATS NIH HHS UL1 TR001863NICHD NIH HHS R01 HD109326
6 · The paper itself

Abstract

CXCR4 is a key regulator of the development of NK cells and DCs, both of which play an important role in early placental development and immune tolerance at the maternal-fetal interface. However, the role of CXCR4 in pregnancy is not well understood. Our study demonstrates that adult-induced global genetic CXCR4 deletion, but not uterine-specific CXCR4 deletion, was associated with increased pregnancy resorptions and decreased litter size. CXCR4-deficient mice had decreased NK cells and increased granulocytes in the decidua, along with increased leukocyte numbers in peripheral blood. We found that CXCR4-deficient mice had abnormal decidual NK cell aggregates and NK cell infiltration into trophoblast areas beyond the giant cell layer. This was associated with low NK cell expression of granzyme B, a NK cell granule effector, indicative of NK cell dysfunction. Pregnancy failure in these mice was associated with abnormalities in placental vascular development and increased placental expression of inflammatory genes. Importantly, adoptive BM transfer of WT CXCR4+ BM cells into CXCR4-deficient mice rescued the reproductive deficits by normalizing NK cell function and mediating normal placental vascular development. Collectively, our study found an important role for maternal CXCR4 expression in immune cell function, placental development, and pregnancy maintenance.

Indexed as

DeciduaPlacentaAnimalsFemaleMicePlacentationPregnancyReceptors, CXCR4Signal TransductionTrophoblastsCXCR4 protein, mouseReceptors, CXCR4Bone marrowChemokinesObstetrics/gynecologyReproductive Biology

Identifiers

PMID37815869
PMCPMC10721256
OpenAlexW4387503458

What OpenQuestion holds

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Registered trials

None linked

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.