ArticlePloS one2014
Small intestinal intraepithelial TCRγδ+ T lymphocytes are present in the premature intestine but selectively reduced in surgical necrotizing enterocolitis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- The gut-brain ConNECtion: exploring the developmental impact of necrotizing enterocolitis on the neonatal brain.Pediatric research · 2026Review
- Temporal mapping of epithelial vs. immune cell inflammatory shifts in the neonatal intestinal mucosa.Pediatric research · 2026Article
- Murine intestinal epithelial cells and lymphocytes undergo contrasting inflammatory shifts during gastrointestinal development.Pediatric research · 2026Article
- The microbiome's hidden influence: preclinical insights into inflammatory responses in necrotizing enterocolitis.Seminars in immunopathology · 2025Review
- The Nonbacterial Infant Microbiome and Necrotizing Enterocolitis.American journal of perinatology · 2025Review
- Necrotizing Enterocolitis: A Comprehensive Review on Toll-like Receptor 4-Mediated Pathophysiology, Clinical, and Therapeutic Insights.Biomedicines · 2025Review
- Tight junction proteins and intestinal health in preterm infants.Journal of neonatal-perinatal medicine · 2025Review
- Predictive value of biomarkers in neonatal necrotizing enterocolitis.Frontiers in pediatrics · 2025Review
- Immunological aspects of necrotizing enterocolitis models: a review.Frontiers in immunology · 2024Review
- Role of innate T cells in necrotizing enterocolitis.Frontiers in immunology · 2024Review
- Development of the Neonatal Intestinal Barrier, Microbiome, and Susceptibility to NEC.Microorganisms · 2023Review
- Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis.PLoS biology · 2023Article
- Neurodevelopmental outcome of infants who develop necrotizing enterocolitis: The gut-brain axis.Seminars in perinatology · 2023Article
- Ontogeny of RORγtCell & bioscience · 2022Article
- Necrotizing enterocolitis: Bench to bedside approaches and advancing our understanding of disease pathogenesis.Frontiers in pediatrics · 2022Review
- Peripheral and intestinal mucosal-associated invariant T cells in premature infants with necrotizing enterocolitis.Frontiers in pharmacology · 2022Article
- Cellular Immune Signal Exchange From Ischemic Stroke to Intestinal Lesions Through Brain-Gut Axis.Frontiers in immunology · 2022Review
- Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage.Cell host & microbe · 2021Article
- CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants.The Journal of experimental medicine · 2021Article
- Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis.Nature communications · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors.
Funding
Abstract
backgroundGastrointestinal barrier immaturity predisposes preterm infants to necrotizing enterocolitis (NEC). Intraepithelial lymphocytes (IEL) bearing the unconventional T cell receptor (TCR) γδ (γδ IEL) maintain intestinal integrity and prevent bacterial translocation in part through production of interleukin (IL) 17.
objectiveWe sought to study the development of γδ IEL in the ileum of human infants and examine their role in NEC pathogenesis. We defined the ontogeny of γδ IEL proportions in murine and human intestine and subjected tcrδ-/- mice to experimental gut injury. In addition, we used polychromatic flow cytometry to calculate percentages of viable IEL (defined as CD3+ CD8+ CD103+ lymphocytes) and the fraction of γδ IEL in surgically resected tissue from infants with NEC and gestational age matched non-NEC surgical controls.
resultsIn human preterm infants, the proportion of IEL was reduced by 66% in 11 NEC ileum resections compared to 30 non-NEC controls (p<0.001). While γδ IEL dominated over conventional αβ IEL early in gestation in mice and in humans, γδ IEL were preferential decreased in the ileum of surgical NEC patients compared to non-NEC controls (50% reduction, p<0.05). Loss of IEL in human NEC was associated with downregulation of the Th17 transcription factor retinoic acid-related orphan nuclear hormone receptor C (RORC, p<0.001). TCRδ-deficient mice showed increased severity of experimental gut injury (p<0.05) with higher TNFα expression but downregulation of IL17A.
conclusionComplimentary mouse and human data suggest a role of γδ IEL in IL17 production and intestinal barrier production early in life. Specific loss of the γδ IEL fraction may contribute to NEC pathogenesis. Nutritional or pharmacological interventions to support γδ IEL maintenance in the developing small intestine could serve as novel strategies for NEC prevention.
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