ArticleCellular and molecular life sciences : CMLS2022
An imbalance of the IL-33/ST2-AXL-efferocytosis axis induces pregnancy loss through metabolic reprogramming of decidual macrophages.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Association of Interleukin-33 with Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis Study.International journal of fertility & sterility · 2025Pooled it
- The IL-33/ST2 pathway to modulate the inflammatory microenvironment: A new therapeutic target in chronic obstructive pulmonary disease.Biochemistry and biophysics reports · 2026Review
- Artificial Intelligence in Recurrent Pregnancy Loss: From Risk Prediction to ART Translation.Journal of clinical medicine · 2026Review
- Trophoblast aging driven by IL33 deficiency elevates recurrent pregnancy loss risk through SNAP29 lactylation-mediated autophagy impairment.Autophagy · 2026Article
- ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Early Pregnancy with Subclinical Hypothyroidism.Biochemical genetics · 2026Article
- Metabolic Reprogramming Driven by Trophoblasts and Decidual XCR1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Untargeted metabolomic profiling of hydrosalpinx fluid: a descriptive analysis with pelvic fluid as external reference.Frontiers in endocrinology · 2026Article
- IL-33 promotes efferocytosis by peritoneal macrophages by a mechanism associated with rapid granulocyte IL-13 production.Frontiers in immunology · 2026Article
- A Machine Learning Model for Predicting Recurrent Pregnancy Loss: Retrospective Integration of Routine Serum IL-33, C-Reactive Protein, and Lymphocyte Subset Counts.International journal of general medicine · 2026Article
- Impact of endocrine disrupting chemicals on macrophages at the maternal-fetal interface.Seminars in immunopathology · 2025Review
- Leukocyte dynamics in female reproductive health: roles and mechanisms.Annals of medicine and surgery (2012) · 2025Review
- Mitochondrial dysfunction in pregnancy loss: a review.Molecular and cellular biochemistry · 2025Review
- The efferocytosis process in aging: Supporting evidence, mechanisms, and therapeutic prospects for age-related diseases.Journal of advanced research · 2025Review
- Perturbations of the endometrial immune microenvironment in endometriosis and adenomyosis: their impact on reproduction and pregnancy.Seminars in immunopathology · 2025Review
- Immunomodulatory effect of efferocytosis at the maternal-fetal interface.Cell communication and signaling : CCS · 2025Review
- Article
- Alarmins and their pivotal role in the pathogenesis of spontaneous abortion: insights for therapeutic intervention.European journal of medical research · 2024Review
- Upregulation ofEpigenetics · 2024Article
- Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.Cell proliferation · 2024Article
- Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages.Biology of sex differences · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
During embryo implantation, apoptosis is inevitable. These apoptotic cells (ACs) are removed by efferocytosis, in which macrophages are filled with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to the relationship between efferocytosis-related metabolism and the immune behavior of decidual macrophages (dMΦs) and its effect on pregnancy outcome. Here, we report positive feedback of IL-33/ST2-AXL-efferocytosis leading to pregnancy failure through metabolic reprogramming of dMΦs. We compared the serum levels of IL-33 and sST2, along with IL-33 and ST2, efferocytosis and metabolism of dMΦs, from patients with normal pregnancies and unexplained recurrent pregnancy loss (RPL). We revealed disruption of the IL-33/ST2 axis, increased apoptotic cells and elevated efferocytosis of dMΦs from patients with RPL. The dMΦs that engulfed many apoptotic cells secreted more sST2 and less TGF-β, which polarized dMΦs toward the M1 phenotype. Moreover, the elevated sST2 biased the efferocytosis-related metabolism of RPL dMΦs toward oxidative phosphorylation and exacerbated the disruption of the IL-33/ST2 signaling pathway. Metabolic disorders also lead to dysfunction of efferocytosis, resulting in more uncleared apoptotic cells and secondary necrosis. We also screened the efferocytotic molecule AXL regulated by IL-33/ST2. This positive feedback axis of IL-33/ST2-AXL-efferocytosis led to pregnancy failure. IL-33 knockout mice demonstrated poor pregnancy outcomes, and exogenous supplementation with mouse IL-33 reduced the embryo losses. These findings highlight a new etiological mechanism whereby dMΦs leverage immunometabolism for homeostasis of the microenvironment at the maternal-fetal interface.
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Registered trials
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.