Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis
Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis
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DOI：
10.1152/ajpgi.00038.2014
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发表时间：
2014-07-15
影响因子：
4.5
通讯作者：
Rhoads, J. Marc
中科院分区：
文献类型：
--
作者：
Liu, Yuying;Tran, Dat Q.;Rhoads, J. Marc
坏死性小肠结肠炎（NEC）是一种炎症性疾病，有证据表明肠黏膜促炎细胞因子的产生增加。罗伊氏乳杆菌DSM 17938 （LR17938）已在NEC实验模型中被证明具有抗炎活性。激活效应淋巴细胞募集到炎症部位需要粘附分子如CD44的连续参与。CD44+CD45RB（lo）的表型将T效应/记忆（Tern）细胞与初始(CD44（-)CD45RB(hi)）细胞分开。目前尚不清楚这些Tem细胞是否参与与NEC相关的炎症，是否可以被LR17938改变。在8 ~ 10日龄C57BL/6J小鼠中，采用配方野蛮喂养和缺氧冷应激4 d诱导NEC。分析生存曲线和组织学评分。从肠系膜淋巴结和回肠中分离淋巴细胞进行CD4、CD4、CD45RB、细胞内Foxp3和Helios标记，并进行流式细胞术分析。L1217938降低了NEC的死亡率、发病率和严重程度。实验组回肠和肠系膜淋巴结的Tern细胞百分比升高，LR17938降低。相反，在NEC期间，肠道中CD4(+)Foxp3（+）调节性T （Treg）细胞的百分比下降，并通过LR17938恢复到正常水平。LR17938保存的Treg细胞大部分为Helios亚群，可能起源于胸腺。总之，LR17938可能是预防NEC的有效治疗方法。LR17938的保护机制涉及调节Tem和Treg细胞之间的平衡。这些T细胞亚群可能是肠道炎症期间潜在的生物标志物和治疗靶点。
Necrotizing enterocolitis (NEC) is an inflammatory disease with evidence of increased production of proinflammatory cytokines in the intestinal mucosa. Lactobacillus reuteri DSM 17938 (LR17938) has been shown to have anti-inflammatory activities in an experimental model of NEC. Activated effector lymphocyte recruitment to sites of inflammation requires the sequential engagement of adhesion molecules such as CD44. The phenotype of CD44+CD45RB(lo) separates T effector/memory (Tern) cells from naive (CD44(-)CD45RB(hi)) cells. It is unknown whether these Tem cells participate in the inflammation associated with NEC and can be altered by LR17938. NEC was induced in 8- to 10-day-old C57BL/6J mice by savage feeding with formula and exposure to hypoxia and cold stress for 4 days. Survival curves and histological scores were analyzed. Lymphocytes isolated from mesenteric lymph nodes and ileum were labeled for CD4, CD4, CD45RB, intracellular Foxp3, and Helios and subsequently analyzed by flow cytom.etry. L1217938 decreased mortality and the incidence and severity of NEC. The percentage of Tern cells in the ileum and mesenteric lymph nodes was increased in NEC but decreased by LR17938. Conversely, the percentage of CD4(+)Foxp3(+) regulatory T (Treg) cells in the intestine decreased during NEC and was restored to normal by LR17938. The majority of the Treg cells preserved by LR17938 were Helios' subsets, possibly of thymic origin. In conclusion, LR17938 may represent a useful treatment to prevent NEC. The mechanism of protection by LR17938 involves modulation of the balance between Tem and Treg cells. These T cell subsets might be potential biomarkers and therapeutic targets during intestinal inflammation.