Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice.
Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice.
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派尔氏集结在非甾体类抗炎药引起的小鼠肠病中发挥保护作用。
DOI：
10.1097/mib.0000000000000017
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Takehara T.
中科院分区：
文献类型：
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作者：
Hiyama S;Iijima H;Shinzaki S;Inoue T;Shiraishi E;Kawai S;Araki M;Kato M;Hayashi Y;Nishida T;Fujii H;Mukai A;Shibata N;Sato S;Kiyono H;Gotoh K;Motooka D;Nakamura S;Iida T;Tsujii M;Takehara T.
背景派伊尔集合淋巴结（Peyer's patches，PP）在粘膜免疫中起重要作用。然而，他们在非甾体抗炎药引起的肠病的作用知之甚少。MethodsWild-type（WT）和PP-null小鼠注射吲哚美辛。24小时后，测量PP、肠系膜淋巴结（MLN）和小肠固有层（LP）中的细胞特征和细胞因子水平。在吲哚美辛治疗之前给予WT和PP缺失小鼠抗生素以评估肠病。将初始CD 4 +T细胞与CD 103+或CD 103 −树突状细胞（DC）共培养，以分析白细胞介素（IL）-10表达水平。最后，野生型小鼠过继转移与CD 103+或CD 103 −DCs注射消炎痛indomethacin.ResultsThe比例的CD 103 +DCs在PPs和MLNs和IL-10表达的CD 4 +T细胞的PPs和LP增加消炎痛治疗后。与野生型小鼠相比，PP基因敲除小鼠表现出更大的吲哚美辛诱导的肠病，MLN中更少的CD 103 + DC，以及LP中表达IL-10的CD 4 +T细胞的比例更低，而与肠道细菌无关。与CD 103 −DCs共培养的脾脏CD 4 +T细胞相比，与从注射吲哚美辛的WT小鼠的MLN分离的CD 103 +DCs共培养的幼稚脾脏CD 4 +T细胞产生更高量的IL-10。此外，野生型小鼠，接受CD 103 + DC表现出较轻的肠病比那些接受CD 103 −DCs.ConclusionsPPs发挥保护作用，在非甾体抗炎药诱导的肠病，这种保护与增加CD 103 + DC和IL-10产生的CD 4 +T细胞在肠道，独立的肠道细菌。
BackgroundPeyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug–induced enteropathy are poorly understood.MethodsWild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina propria (LP) of the small intestine were measured. WT and PP-null mice were given antibiotics before indomethacin treatment to evaluate enteropathy. Naive CD4+T cells were co-cultured with CD103+or CD103−dendritic cells (DCs) to analyze the interleukin (IL)-10 expression levels. Finally, WT mice adoptively transferred with CD103+or CD103−DCs were injected with indomethacin.ResultsThe proportion of CD103+DCs in PPs and MLNs and IL-10-expressing CD4+T cells of PPs and the LP increased after indomethacin treatment. The PP-null mice showed greater indomethacin-induced enteropathy, fewer CD103+DCs in their MLNs, and lower proportion of IL-10-expressing CD4+T cells of their LP than WT mice, regardless of commensal bacteria. Naive splenic CD4+T cells co-cultured with CD103+DCs isolated from the MLNs of indomethacin-injected WT mice produced a higher amount of IL-10 compared with those co-cultured with CD103−DCs. Moreover, WT mice that received CD103+DCs showed milder enteropathy than those that received CD103−DCs.ConclusionsPPs play a protective role in nonsteroidal anti-inflammatory drug–induced enteropathy, and this protection is associated with an increase in CD103+DCs and IL-10-producing CD4+T cells in the intestine, independent of the commensal bacteria.