Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios.

Weitkamp JH, Koyama T, Rock MT, Correa H, Goettel JA, Matta P, Oswald-Richter K, Rosen MJ, Engelhardt BG, Moore DJ, Polk DB
Gut. 2013 62 (1): 73-82

PMID: 22267598 · PMCID: PMC3606820 · DOI:10.1136/gutjnl-2011-301551

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.

MeSH Terms (18)

Biomarkers Case-Control Studies CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Enterocolitis, Necrotizing Female Flow Cytometry Forkhead Transcription Factors Gene Expression Profiling Humans Infant, Newborn Infant, Premature Infant, Premature, Diseases Intestinal Mucosa Lymphocyte Count Male Prospective Studies T-Lymphocytes, Regulatory

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