ArticleThe Journal of clinical investigation2019
CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 72 citations in OpenAlex.
- NKR-P1A/CD161: A Multifunctional Immune Receptor at the Crossroads of Antitumor Immunity.Biomolecules · 2026Review
- Immune development in early life.Nature immunology · 2026Review
- Abnormal Pro-inflammatory Immune Cell Responses Precede Clinical Onset of Hypertensive Disorders of Pregnancy.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Underexplored maternal microbiomes: immune, metabolic, and microbial pathways shaping pregnancy outcomes.Infection and immunity · 2026Review
- TCR repertoire shaping of naïve T cell subsets in human ontogeny.Frontiers in immunology · 2026Article
- Evidence for Maternal Autoantibodies in the Pathogenesis of Preterm Birth.medRxiv : the preprint server for health sciences · 2025Article
- Epigenetic instability and hypofunctionality of fetal Tregs allow a permissive regulatory environment for T effector memory maturation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Rational adjuvant selection for the neonatal period shapes unique and lasting immune polarization in mice.NPJ vaccines · 2025Article
- Lifelong partners: Gut microbiota-immune cell interactions from infancy to old age.Mucosal immunology · 2025Review
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- The maternal-fetal interface at single-cell resolution: uncovering the cellular anatomy of the placenta and decidua.American journal of obstetrics and gynecology · 2025Review
- Shaping immunity: the influence of the maternal gut bacteria on fetal immune development.Seminars in immunopathology · 2025Review
- Immunobiology roles of the human CD161 receptor in T cells.Frontiers in immunology · 2025Review
- Single-cell atlas of the small intestine throughout the human lifespan demonstrates unique features of fetal immune cells.Mucosal immunology · 2024Article
- The maternal gut microbiome in pregnancy: implications for the developing immune system.Nature reviews. Gastroenterology & hepatology · 2024Review
- Blockade of IL-6R prevents preterm birth and adverse neonatal outcomes.EBioMedicine · 2023Article
- Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans.JCI insight · 2023Article
- Contributions of the early-life microbiome to childhood atopy and asthma development.Seminars in immunology · 2023Review
- MAITs and their mates: "Innate-like" behaviors in conventional and unconventional T cells.Clinical and experimental immunology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundWhile the human fetal immune system defaults to a program of tolerance, there is concurrent need for protective immunity to meet the antigenic challenges encountered after birth. Activation of T cells in utero is associated with the fetal inflammatory response with broad implications for the health of the fetus and of the pregnancy. However, the characteristics of the fetal effector T cells that contribute to this process are largely unknown.
methodsWe analyzed primary human fetal lymphoid and mucosal tissues and performed phenotypic, functional, and transcriptional analysis to identify T cells with pro-inflammatory potential. The frequency and function of fetal-specific effector T cells was assessed in the cord blood of infants with localized and systemic inflammatory pathologies and compared to healthy term controls.
resultsWe identified a transcriptionally distinct population of CD4+ T cells characterized by expression of the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF). PLZF+ CD4+ T cells were specifically enriched in the fetal intestine, possessed an effector memory phenotype, and rapidly produced pro-inflammatory cytokines. Engagement of the C-type lectin CD161 on these cells inhibited TCR-dependent production of IFNγ in a fetal-specific manner. IFNγ-producing PLZF+ CD4+ T cells were enriched in the cord blood of infants with gastroschisis, a natural model of chronic inflammation originating from the intestine, as well as in preterm birth, suggesting these cells contribute to fetal systemic immune activation.
conclusionOur work reveals a fetal-specific program of protective immunity whose dysregulation is associated with fetal and neonatal inflammatory pathologies.
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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 Socratic graph.