Department of Pediatrics, The University of Texas Medical School, Houston, Texas, United States of America.
PLoS One. 2013 Dec 18;8(12):e82963. doi: 10.1371/journal.pone.0082963. eCollection 2013.
Necrotizing enterocolitis (NEC) results from severe intestinal inflammation in premature infants. FoxP3(+) regulatory T cells (Tregs) are central to gut homeostasis. While Treg proportions are significantly reduced in the ileums of premature infants with NEC, it is unknown whether they play a critical function in preventing NEC. This study investigated Treg development in newborn rat pups and their role in experimental NEC induction. Utilizing an established rat model of experimental NEC, the ontogeny of T cells and Tregs in newborn pups was characterized by flow cytometry. To investigate the functions of Tregs, newborn pups were given Tregs harvested from adult rats prior to NEC induction to assess clinical improvement and mechanisms of immune regulation. The results revealed that there were few Treg numbers in the terminal ileums of newborn rats and 8-fold reduction after NEC. Adoptive transfer of Tregs significantly improved weight loss, survival from 53% to 88%, and NEC incidence from 87% to 35%. The Tregs modulated the immune response as manifested in reduced CD80 expression on antigen presenting cells and decreased T cell activation within the mesenteric lymph nodes. These findings suggest that while Tregs are present in the intestines, their numbers might be insufficient to dampen the excessive inflammatory state in NEC. Adoptive transfer of Tregs attenuates the severity of NEC by limiting the immune response. Strategies to enhance Tregs have a therapeutic potential in controlling the development of NEC.
坏死性小肠结肠炎（NEC）是由早产儿严重的肠道炎症引起的。FoxP3(+)调节性 T 细胞（Tregs）是肠道内稳态的核心。虽然 NEC 早产儿回肠中的 Treg 比例显著降低，但尚不清楚它们在预防 NEC 中是否发挥关键作用。本研究旨在探讨新生大鼠 Treg 的发育及其在实验性 NEC 诱导中的作用。利用已建立的实验性 NEC 大鼠模型，通过流式细胞术对新生大鼠 T 细胞和 Treg 的发育进行了特征分析。为了研究 Treg 的功能，在 NEC 诱导前，将从成年大鼠中提取的 Treg 转移到新生大鼠中，以评估临床改善和免疫调节机制。结果表明，新生大鼠回肠中 Treg 数量较少，NEC 后减少 8 倍。Treg 的过继转移可显著改善体重减轻，存活率从 53%提高到 88%，NEC 发生率从 87%降低到 35%。Treg 调节了免疫反应，表现为抗原呈递细胞上 CD80 表达减少，肠系膜淋巴结内 T 细胞活化减少。这些发现表明，尽管 Treg 存在于肠道中，但它们的数量可能不足以抑制 NEC 中过度的炎症状态。Treg 的过继转移通过限制免疫反应来减轻 NEC 的严重程度。增强 Treg 的策略具有控制 NEC 发展的治疗潜力。
