Division 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.
Gut. 2013 Jan;62(1):73-82. doi: 10.1136/gutjnl-2011-301551. Epub 2012 Jan 20.
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.
To investigate the hypothesis that abnormal developmental regulation of lamina propria Treg would define premature infants with NEC.
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.
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.
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.
坏死性小肠结肠炎（NEC）是早产儿最常见的胃肠道急症。胃肠道免疫调节不成熟可能使早产儿易患 NEC，因为 FOXP3+T 调节细胞（Treg）对于肠道免疫稳态至关重要。
研究假设固有层 Treg 的异常发育调节将定义患有 NEC 的早产儿。
前瞻性分离 18 例 NEC 患者和 30 例胎龄匹配的非 NEC 手术对照患者手术切除回肠的固有层单核细胞群体。多色流式细胞术用于表型分析固有层 T 细胞群体。比较 NEC 组织与非 NEC 对照的细胞因子基因表达谱。
每个回肠切片中 Treg、CD4 或 CD8 T 细胞的总数与胎龄、年龄或月经后年龄无关，并且在 NEC 患者和对照组之间相似。相比之下，NEC 回肠中 Treg 与 CD4 T 细胞或 Treg 与 CD8 T 细胞的比值明显低于无 NEC 的婴儿（中位数 2.9%比 6.6%，p=0.001 和中位数 6.6%比 25.9%，p<0.001）。对于任何给定数量的 CD4 或 CD8 T 细胞，NEC 回肠中的 Treg 平均低 60%。NEC 组织细胞因子基因表达谱的特点是 Treg 发育或功能受抑制。Treg/CD4 和 Treg/CD8 比值在 NEC 初次切除与再吻合之间恢复。
患有 NEC 的早产儿固有层 Treg 的比例明显降低，可能导致这种疾病的过度炎症状态。
