Roseburia intestinalis inhibits interleukin‑17 excretion and promotes regulatory T cells differentiation in colitis.

Roseburia intestinalis inhibits interleukin‑17 excretion and promotes regulatory T cells differentiation in colitis.
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肠罗斯氏菌抑制结肠炎中白细胞介素 17 的排泄并促进调节性 T 细胞分化

DOI:
10.3892/mmr.2018.8833
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发表时间:
2018-06
影响因子:
3.4
通讯作者:
Wang X
Wang X
中科院分区:
医学4区
文献类型:
--
作者:
Zhu C;Song K;Shen Z;Quan Y;Tan B;Luo W;Wu S;Tang K;Yang Z;Wang X

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迷迭香是肠道优势菌群之一,在炎症性肠病(IBD)患者中呈下降趋势。它有助于保护结肠粘膜免受炎症和随后的IBD的发展,然而其潜在的机制尚不清楚。本研究的目的是在体外和在IBD动物模型中评价肠黄连的抗炎作用。在2,4,6-三硝基苯磺酸(TNBS)诱导的小鼠结肠炎模型上,观察了肠炎灵芝对疾病活动指数(DAI)评分、肠道病理改变、IL-17表达及CD4+CD25+Foxp3+调节性T细胞(Treg)频率的影响。与对照组相比,经TNBS处理的小鼠具有更高的IL-17分泌、更高的DAI评分、更低的Treg比率、更短的结肠长度和更高的结肠炎症组织学评分。与单纯灌胃TNBS组相比,灌肠给药组小鼠结肠组织中IL-17的表达明显下调,Treg的比例明显增加,DAI评分明显降低,炎症病理改变明显减轻。基因表达谱检测IL-17在人IBD和健康对照标本中的表达。为了将这些发现扩展到体外炎症模型,用脂多糖(LPS)刺激人结肠上皮细胞株NCM460诱导炎症,并与肠杆菌共同培养,观察IL-17表达的变化。肠杆菌可抑制内毒素诱导的NCM460细胞分泌IL-17。综上所述,这些结果表明,肠黄抑制IL-17的分泌,促进Treg在结肠炎中的分化,提示其可能在治疗IBD方面具有潜在的应用价值。
Roseburia intestinalis (R. intestinalis) is one of the dominant intestinal bacterial microbiota and is decreased in patients with inflammatory bowel disease (IBD). It helps protect colonic mucosa against the development of inflammation and subsequent IBD, however its underlying mechanisms are unclear. The aim of the present study was to evaluate the anti-inflammatory properties of R. intestinalis in vitro and in an animal model of IBD. The effects of R. intestinalis on disease activity index (DAI) scores, intestinal pathology, the expression of interleukin (IL)-17 and the frequency of CD4+CD25+Foxp3+ regulatory T cells (Treg) were evaluated in vivo in a model of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis. Compared with the control group, TNBS-treated mice had significantly higher secretion of IL-17, higher DAI scores, a lower ratio of Treg, reduced colon lengths and higher histological scores for colon inflammation. The administration of R. intestinalis significantly downregulated the expression of IL-17, increased the ratio of Treg and ameliorated the high DAI scores and the pathological signs of inflammation in the colon compared with mice treated with TNBS alone. Gene expression profiling was also used to detect the expression of IL-17 in human IBD and healthy control specimens. To extend these findings to an in vitro model of inflammation the human colon epithelial cell line NCM460 was stimulated with lipopolysaccharide (LPS) to induce inflammation and co-cultured with R. intestinalis and changes in IL-17 expression were evaluated. R. intestinalis inhibited the LPS-induced secretion of IL-17 by NCM460 cells. In conclusion, these results demonstrate that R. intestinalis inhibits IL-17 secretion and promotes Treg differentiation in colitis, suggesting that R. intestinalis could be of potential use in the treatment of IBD.
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