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Updated: May 25, 2026

A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Published on: November 30, 2021
Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory
Jörn-Hendrik Weitkamp1, Tatsuki Koyama, Michael T Rock
1Division of Neonatology, Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt, 2215 B Garland Ave., 1125 MRB IV/Light Hall, Nashville, TN 37232-0656, USA. hendrik.weitkamp@vanderbilt.edu
Background:
Necrotising enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. Immaturity of gastrointestinal immune regulation may predispose preterm infants to NEC as FOXP3 T regulatory cells (Treg) are critical for intestinal immune homoeostasis.
Objective:
To investigate the hypothesis that abnormal developmental regulation of lamina propria Treg would define premature infants with NEC.
Design:
Lamina propria mononuclear cell populations from surgically resected ileum from 18 patients with NEC and 30 gestational age-matched non-NEC surgical controls were prospectively isolated. Polychromatic flow cytometry was performed to phenotype and analyse lamina propria T cell populations. The cytokine gene expression profile in NEC tissue was compared with that of non-NEC controls.
Results:
The total number of Treg, CD4, or CD8 T cells in each ileum section was independent of gestational age, age or postmenstrual age and similar between patients with NEC and controls. In contrast, the ratio of Treg to CD4 T cells or Treg to CD8 T cells was significantly lower in NEC ileum than in infants without NEC (medians 2.9% vs 6.6%, p=0.001 and medians 6.6% vs 25.9%, p<0.001, respectively). For any given number of CD4 or CD8 T cells, Treg were, on average, 60% lower in NEC ileum than in controls. NEC tissue cytokine gene expression profiles were characteristic of inhibited Treg development or function. Treg/CD4 and Treg/CD8 ratios recovered between initial resection for NEC and reanastomosis.
Conclusion:
The proportion of lamina propria Treg is significantly reduced in the ileum of premature infants with NEC and may contribute to the excessive inflammatory state of this disease.
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