{"id":261,"title":"IL-33 modulates maternal-fetal macrophage immunometabolism and is associated with attenuation of MIA-associated behavioral abnormalities in adult offspring","title_zh":"IL-33通过调节母胎界面巨噬细胞免疫代谢减轻母体免疫激活相关子代行为异常","url":"https://pubmed.ncbi.nlm.nih.gov/42971914","doi":"10.7555/jbr.40.20260347","pmid":"42971914","journal":"J Biomed Res","kind":"paper","lang":"en","published_at":"2026-10-25T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Zhu X","Shen C","He K","Chang H","Qiu J","Chen L","Chen L","Hou M","Ji M","Xu Z"],"primary_topic":"repro-immunology","topics":[{"slug":"repro-immunology","score":5.0,"hits":["macrophage","maternal immune"]},{"slug":"endometrium","score":2.0,"hits":["maternal-fetal interface","placental"]},{"slug":"repro-aging","score":1.0,"hits":["mitochondrial"]},{"slug":"omics-methods","score":1.0,"hits":["proteomic"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":74.0,"final_score":74.0,"score_dims":{"novelty":78,"rigor":68,"impact":66,"relevance":62,"translation":45},"recommend_reason":"首次从母胎界面巨噬细胞免疫代谢角度串联IL-33/ST2与MIA相关子代神经行为结局，并辅以ST2缺陷验证，机制链条较完整；但为小鼠模型、探索性设计，与ART临床决策距离较远，适合关注生殖免疫与母胎界面的读者浏览。","keywords":["IL-33/ST2","母体免疫激活","母胎界面","巨噬细胞免疫代谢","胎盘炎症","神经发育"],"selected":1,"story_id":330,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-uterus-pregnancy","source_name":"PubMed · 内膜/植入/早孕","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"研究以弓形虫可溶性速殖子抗原（STAg）在妊娠E14.5诱导小鼠母体免疫激活（MIA），并于E15.5–E17.5给予母体IL-33。蛋白组学与蛋白互作网络分析提示IL-33为候选免疫调节因子；探索性分析显示母体IL-33干预与巨噬细胞免疫表型改变、胎盘炎症减轻及成年子代MIA相关行为异常减弱相关。ST2缺陷小鼠中上述巨噬细胞复极化与炎症稳态效应消失，行为改善亦不明显。机制上IL-33与巨噬细胞糖酵解特征降低、线粒体功能改善相关，提示母胎界面免疫代谢稳态部分恢复，IL-33/ST2轴为潜在实验靶点。","summary":"Maternal immune activation (MIA) is a pivotal risk factor for neurodevelopmental disorders, including autism spectrum disorder. However, the mechanisms of MIA at the maternal-fetal interface remain elusive. Here, we used soluble tachyzoite antigen (STAg) from Toxoplasma gondii to induce MIA in pregnant mice at E14.5, followed by maternal administration of interleukin-33 (IL-33) from E15.5 to E17.5. Proteomic profiling coupled with protein-protein interaction network analysis nominated IL-33 as a candidate immunoregulatory factor. In exploratory analyses, maternal IL-33 administration was associated with shifts in macrophage-associated immune profiles, reduced placental inflammation, and attenuated MIA-associated behavioral abnormalities in adult offspring. Given that suppression of tumorigenicity 2 (ST2) is the cognate receptor for IL-33, we next interrogated this pathway in ST2-deficient mice. ST2 deficiency abolished the effects of IL-33 on macrophage repolarization and inflammatory homeostasis, and the behavioral improvements were not evident in ST2-deficient offspring. Mechanistically, IL-33 administration was associated with reduced glycolytic features and improved mitochondrial function in macrophages, consistent with partial restoration of immunometabolic homeostasis at the maternal-fetal interface. Collectively, our findings highlight an immunometabolic axis in STAg-induced MIA pathogenesis, revealing IL-33/ST2 signaling as a potential experimental target for mitigating MIA-associated immune and behavioral abnormalities.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}