Mechanisms of L. reuteri in regulating intestinal inflammation

NIH NCCAM RFA-AT-11-001 罗氏乳杆菌调节肠道炎症的作用机制 Pi：Marc Rhoads医学博士和刘玉英博士 摘要 鲁氏乳杆菌(LR)对几种人类疾病有有益的作用。坏死性 小肠结肠炎(NEC)是最常见的严重胃肠道疾病，影响7%的人 早产儿。我们的初步研究表明，在新生小鼠中， NEC认为，喂食LR可降低死亡率和肠道炎症，同时增加肠道 粘膜调节性T细胞(Tregs)，具有抗炎特性的细胞。 具体目标： 1.确定LR是否促进耐受树突状细胞(DC)的产生 DC(前哨细胞)上的细菌识别受体称为Toll样受体(TLRs)。肠 炎症被认为是通过DC与粘膜辅助T细胞(Th1)的相互作用来维持的 和Th17)，并由Tregs减少。我们将衡量NEC的严重程度，对LR的反应， TLRs基因缺陷小鼠的Tregs、Th1和Th17效应器的百分比。 2.阐明LR条件树突状细胞是否能更有效地抑制Th1/Th17效应。 对于发炎的肠道，我们将从LR-Feed中过继转移带有同源标记的Tregs 小鼠到新生小鼠接受NEC，以确定外源Tregs是否具有保护作用。 3.确定LR是否能够在肠粘膜中诱导Tregs(ITregs) 当天然树突状细胞(NTreg)耗尽时，我们会通过抗CD25抗体和 确定LR是否促进iTreg发育并保持减少肠道发育的能力 发炎。 这些目的将为研究鲁氏乳杆菌调节细胞生长的机制提供新的见解。 新生儿肠炎。结果将有助于选择符合以下要求的生物标志物 NEC的进化并比较不同益生菌在人类婴儿中的效力。

NIH NCCAM RFA-AT-11-001 Mechanisms of L. reuteri in regulating intestinal inflammation PI: Marc Rhoads, MD and Yuying Liu, PhD Abstract Lactobacillus reuteri (LR) has beneficial effects in several human diseases. Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal condition affecting 7% of premature infants. Our preliminary studies demonstrated in neonatal mice with experimental NEC that LR feeding reduces mortality and intestinal inflammation, while increasing intestinal mucosal regulatory T cells (Tregs), cells with anti-inflammatory properties. Specific Aims: 1. To determine whether LR facilitates the generation of tolerogenic dendritic cells (DCs) via bacterial recognition receptors on DC ("sentinel cells") called Toll like receptors (TLRs). Gut inflammation is believed to be sustained by DC interaction with mucosal helper T cells (Th1 and Th17) and reduced by Tregs. We will measure NEC severity, response to LR, percentage of Tregs, Th1, and Th17 effectors in mice genetically deficient in TLRs. 2. To elucidate if LR-conditioned Tregs will be more efficient to suppress Th1/Th17 effectors in the inflamed gut, we will adoptively transfer Tregs bearing congenic markers from LR-fed mice to newborn mice undergoing NEC to determine if exogenous Tregs protect. 3. To determine whether LR is capable of inducing Tregs (iTregs) in the intestinal mucosa when natural Tregs (nTreg) are depleted, we will deplete nTregs by anti-CD25 antibody and determine if LR enhances iTreg development and remains capable of reducing intestinal inflammation. These Aims will provide novel insights into mechanisms of Lactobacillus reuteri regulation of neonatal intestinal inflammation. Results will facilitate the selection of biomarkers to follow the evolution of NEC and to compare the potency of different probiotics in the human infant.