Oral Escherichia coli expressing IL-35 meliorates experimental colitis in mice.
Oral Escherichia coli expressing IL-35 meliorates experimental colitis in mice.
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口服表达 IL-35 的大肠杆菌可改善小鼠实验性结肠炎
DOI：
10.1186/s12967-018-1441-7
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发表时间：
2018-03-20
影响因子：
7.4
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhang B;Liu Y;Lan X;Xu X;Zhang X;Li X;Zhao Y;Li G;Du C;Lu S;Wang H
背景：溃疡性结肠炎（UC）是一种以结肠慢性炎症为特征的炎症性肠病（IBD）。一般认为UC的发病机制与免疫系统失衡和细胞因子分泌过多有关。最近的研究表明，白细胞介素-35 （IL-35）在炎症的调节中起着关键作用，已被确定为治疗UC的潜在治疗靶点。然而，传统的静脉给药既昂贵又不方便。本研究旨在建立一种新型IL-35给药系统，并首次探讨其对葡聚糖硫酸钠（DSS）诱导小鼠实验性结肠炎的治疗作用。方法：构建表达IL-35的工程大肠杆菌（E. coli/IL-35）。成年雄性BALB/c小鼠在摄入3% DSS溶液后，随机口服大肠杆菌/IL-35、空质粒转化大肠杆菌（E. coli0）或PBS治疗5 d。以正常小鼠为对照组。dss诱导后第10天收集结肠和脾组织。评估临床症状、疾病活动指数（DAI）、病理和免疫组织学变化、细胞因子谱和细胞群。结果：大肠杆菌/IL-35灌胃可有效保护结肠炎小鼠的DSS同化，包括体重减轻和结肠缩短。病理分析显示，IL-35治疗组DAI评分明显降低，结肠内中性粒细胞和CD3+细胞浸润明显减少。此外，大肠杆菌/IL-35处理小鼠脾脏和肠系膜淋巴结CD4+IL-17A+Th17细胞明显减少，CD4+CD25+Foxp3+Tregs细胞水平升高，结肠和血清IL-10和IL-35水平升高，IL-6水平降低。结论：我们的研究表明，大肠杆菌/IL-35作为一种新型的口服IL-35递送系统，可以减轻结肠炎小鼠结肠组织的炎症损伤。利用工程大肠杆菌编码免疫调节细胞因子的基因治疗策略可能为治疗IBD提供一种潜在的方法。
Background:Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by chronic inflammation of colon. It is commonly believed that the imbalance of immune system and overwhelming production of cytokines are involved in the pathogenesis of UC. Recent studies demonstrated that interleukin-35 (IL-35), a key player in the regulation of inflammation, has been identified as potential therapeutic target to treat UC. However, conventional intravenous administration is costly and inconvenient. The present study was designed to establish a novel IL-35 delivery system and investigate its therapeutic effects on dextran sulfate sodium (DSS)-induced experimental colitis in mice for the first time.Methods:An engineered Escherichia coli (E. coli/IL-35) expressing IL-35 was constructed. Adult male BALB/c mice randomly got the oral administration of E. coli/IL-35, empty plasmid-transformed E. coli (E. coli0) or PBS for treatment following ingestion of 3% DSS solution for 5 days. Normal mice were used as control group. Colonic and splenic tissues were collected on day 10 post-DSS-induction. Clinical signs, disease activity index (DAI), pathological and immunohistological changes, cytokine profiles and cell populations were evaluated.Results:Intragastric administration of E. coli/IL-35 effectively protected the colitis mice from DSS assimilation including weight loss and colon shortening. Pathological analysis showed significantly lower DAI score and much less intra-colon infiltration of neutrophils and CD3+cells in the IL-35 treated group. Moreover, E. coli/IL-35-treated mice demonstrated much less CD4+IL-17A+Th17 cells and a higher level of CD4+CD25+Foxp3+Tregs in spleen and mesenteric lymph nodes, as well as increased colon and serum level of IL-10 and IL-35 and decreased levels of IL-6.Conclusions:Our study showed that E. coli/IL-35 as a novel oral IL-35 delivery system alleviated inflammatory damage of colonic tissue in the colitic mice. Genetic therapeutic strategies using engineered E. coli encoding immunoregulatory cytokines may provide a potential approach for the treatment of IBD.
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影响因子：
29.4
作者：
Ng, Siew C.;Tang, Whitney;Chan, Francis K. L.
通讯作者：
Chan, Francis K. L.
影响因子：
7.4
作者：
Lv Y;Xu X;Zhang B;Zhou G;Li H;Du C;Han H;Wang H
通讯作者：
Wang H
影响因子：
5.4
作者：
Niedbala, Wanda;Wei, Xiao-qing;Liew, Foo Y.
通讯作者：
Liew, Foo Y.
DOI：
10.1007/s00005-009-0031-z
发表时间：
2009-08-01
影响因子：
3.2
作者：
Szkaradkiewicz, Andrzej;Marciniak, Ryszard;Zwozdziak, Barbara
通讯作者：
Zwozdziak, Barbara
影响因子：
4.9
作者：
McLean MH;Neurath MF;Durum SK
通讯作者：
Durum SK