Regulatory T Cells Restrict Permeability to Bacterial Antigen Translocation and Preserve Short-Chain Fatty Acids in Experimental Cirrhosis
Regulatory T Cells Restrict Permeability to Bacterial Antigen Translocation and Preserve Short-Chain Fatty Acids in Experimental Cirrhosis
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DOI：
10.1002/hep4.1268
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发表时间：
2018-12-01
影响因子：
5.1
通讯作者：
Frances, Ruben
中科院分区：
文献类型：
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作者：
Juanola, Oriol;Pinero, Paula;Frances, Ruben
肝硬化患者肠道对细菌产物转运的通透性增加。调节性T细胞（Tcells）仍然是宿主和微生物环境之间相互作用的核心。我们认为，TCFs参与促进肠道屏障的完整性和平衡的相互作用与肠道微生物来源的短链脂肪酸（SCFA）。在野生型和重组激活基因1（Rag 1）（-）（/-）小鼠中诱导四氯化碳肝硬化。将初始T细胞和Treg细胞转移到Rag 1（-）（/-）小鼠中。在脂多糖（LPS）口服给药后，在体内评估肠道通透性，并在肠系膜淋巴结中评估细菌DNA的存在。在结肠组织中测量紧密连接（TJ）蛋白的转录物和蛋白水平。肠道辅助性T细胞对大肠杆菌（E。coli）进行流式细胞术测定。用气相色谱-质谱法测定大肠杆菌感染前后结肠内容物中SCFAs的含量。大肠杆菌攻毒。Rag 1（-）（/-）小鼠对LPS的通透性和细菌DNA易位率均显著高于对照组。在Rag 1（-）（/-）小鼠中，初始T和Treg共转移显著降低了肠道对细菌抗原易位的通透性，并恢复了TJ蛋白表达。在Rag 1（-）（/-）小鼠中补充初始T和Treg抑制肠淋巴细胞对E.杆菌主要SCFA浓度导致E. coli给药，但在幼稚T和T细胞共转移后保持不变。E.在Rag 1（-）（/-）小鼠中，在幼稚T和Treg重建后重建大肠杆菌。结论：肠道通透性的限制、局部炎症分化和细菌源性SCFA的丧失促进了THBE在肝硬化中预防细菌移位的价值。
Intestinal permeability to translocation of bacterial products is increased in cirrhosis. Regulatory T cells (Tregs) remain central to the interplay between the host and microbial milieu. We propose that Tregs are involved in promoting gut barrier integrity and a balanced interaction with gut microbiota-derived short-chain fatty acids (SCFAs). Carbon tetrachloride cirrhosis was induced in wild-type and recombination activating gene 1 (Rag1)(-)(/-) mice. Naive T cells and Treg cells were transferred into Rag1(-)(/-) mice. Intestinal permeability was assessed in vivo after lipopolysaccharide (LPS) oral administration, and bacterial DNA presence was evaluated in mesenteric lymph nodes. Transcript and protein levels of tight-junction (TJ) proteins were measured in colonic tissue. Intestinal T helper profile in response to Escherichia coli (E. coli) was determined by flow cytometry. SCFAs were measured by gas chromatography-mass spectrometry in colonic content before and after E. coli challenge. Rag1(-)(/-) mice showed significantly increased permeability to LPS and bacterial DNA translocation rate compared with control mice. Naive T and Treg cotransfer significantly reduced gut permeability to bacterial antigen translocation and restored TJ protein expression in Rag1(-)(/-) mice. Naive T and Treg replenishment in Rag1(-)(/-) mice restrained proinflammatory differentiation of intestinal lymphocytes in response to E. coli. The main SCFA concentration resulted in significant reduction in Rag1(-)(/-) mice after E. coli administration but remained unaltered after naive T and Tregs cotransfer. The reduced expression of SCFA receptors induced by E. coli was reestablished following naive T and Treg reconstitution in Rag1(-)(/- )mice. Conclusion: The restriction of gut permeability, local inflammatory differentiation, and loss of bacteria-derived SCFAs foster the value of Tregs in preventing bacterial translocation in cirrhosis.