ArticleCell death & disease2014
IFN-γ induces aberrant CD49b⁺ NK cell recruitment through regulating CX3CL1: a novel mechanism by which IFN-γ provokes pregnancy failure.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Immunological Indicators of Recurrent Pregnancy Loss: A Mendelian Randomization Study.Reproductive sciences (Thousand Oaks, Calif.) · 2024Pooled it
- Inhibition of p65 nuclear translocation in decidual stromal cells underlies COS-induced supraphysiologic estrogen impairment of uNK cell function which drives placental abnormalities.Journal of translational medicine · 2026Article
- A Spatiotemporally Controlled Nanoplatform for Photothermal BRD4 Degradation Enables Synergistic Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synergistic immunotherapeutic effects of irreversible electroporation and CAR-NK cell therapy against hepatocellular carcinoma.Signal transduction and targeted therapy · 2026Article
- Fractalkine (Chemokine CX3CL1) Signaling During Placentation and Placental Function.International journal of molecular sciences · 2026Review
- Hyaluronic acid-CD44 signaling from decidual stromal cells orchestrates dNK1 differentiation and immune tolerance in early pregnancy.Frontiers in immunology · 2026Article
- IFN-γ+ NK cells as a potential predictor of pregnancy loss in unexplained recurrent pregnancy loss.International journal of medical sciences · 2026Article
- Cholesterol modified defense peptide as an EMP2-siRNA delivery system for synergistic immunogene therapy against breast cancer.Materials today. Bio · 2025Article
- Dual Role of Natural Killer Cells in Early Pregnancy: Immunopathological Implications and Therapeutic Potential in Recurrent Spontaneous Abortion and Recurrent Implantation Failure.Cell proliferation · 2025Review
- The Effect of Granulocyte Colony-Stimulating Factor on Endometrial Receptivity of Implantation Failure Mouse.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Aberrant CD8Frontiers in immunology · 2024Article
- Article
- Modeling the Progression of Placental Transport from Early- to Late-Stage Pregnancy by Tuning Trophoblast Differentiation and Vascularization.Advanced healthcare materials · 2023Article
- Expression dynamics of Crry at the implantation sites in normal pregnancy and response against miscarriage induction.The Journal of veterinary medical science · 2023Article
- Research progress on the STAT signaling pathway in pregnancy and pregnancy-associated disorders.Frontiers in immunology · 2023Review
- Natural killer cell homing and trafficking in tissues and tumors: from biology to application.Signal transduction and targeted therapy · 2022Review
- Role of chemokines in early pregnancy loss.Experimental and therapeutic medicine · 2022Article
- Cytochrome P450 26A1 regulates the clusters and killing activity of NK cells during the peri-implantation period.Journal of cellular and molecular medicine · 2022Article
- Maternal natural killer cells at the intersection between reproduction and mucosal immunity.Mucosal immunology · 2021Review
- Interferon γ neutralization reduces blood pressure, uterine artery resistance index, and placental oxidative stress in placental ischemic rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-γ (IFN-γ), a pleiotropic lymphokine, has important regulatory effects on many cell types. Although IFN-γ is essential for the initiation of uterine vascular modifications and maintenance of decidual integrity, IFN-γ administration can also cause pregnancy failure in many species. However, little is known about the effector mechanisms involved. In this study, using an IFN-γ-induced abortion mouse model, we reported that no Dolichos biflorus agglutinin lectin-positive uterine natural killer (uNK) cells were observed in the uteri from IFN-γ-induced abortion mice. By contrast, the percentage of CD3(-)CD49b(+) NK cells in the uterus and blood from a foetal resorption group was significantly higher than that of the control group. Similarly, significantly upregulated expression of CD49b (a pan-NK cell marker), CX3CL1 and CX3CR1 (CX3CL1 receptor) was detected in the uteri of IFN-γ-induced abortion mice. Using isolated uterine stromal cells, we showed that upregulated expression of CX3CL1 by IFN-γ was dependent on a Janus family kinase 2-signal transducers and activators of transcription 1 (JAK2-STAT1) pathway. We further demonstrated the chemotactic activity of CX3CL1 in uterine stromal cell conditioned medium on primary splenic NK cells. Finally, we observed increased recruitment of CD49b(+) NK cells into the endometrium after exogenous CX3CL1 administration. Collectively, our findings indicate that IFN-γ can significantly increase uterine CX3CL1 expression via activation of the JAK2-STAT1 pathway, thus inducing CD49b(+) NK cell uterine homing, and eventually provoke foetal loss. Thus, we provide a new line of evidence correlating the deleterious effects of IFN-γ on pregnancy with the aberrant regulation of CX3CL1 and CD49b(+) NK cells.
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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.