Nat Commun:科学家揭示银屑病发病机理

2015-10-08 佚名 生物谷

银屑病(又称牛皮癣),是发病率高达的2%的炎性皮肤病,然而其发病的具体机制并不十分清楚。最近一些研究表明肠道微生物与自身免疫病的发生之间具有莫大的联系,而具体到银屑病与肠道微生物之间的关系也并不清楚。针对这一问题,来自美国NIH的WanJun Chen课题组做了相关研究,结果发表在最近一期的nature communication 杂志上。之前的研究发现:对小鼠的皮肤与耳部施加imiquimod


银屑病(又称牛皮癣),是发病率高达的2%的炎性皮肤病,然而其发病的具体机制并不十分清楚。最近一些研究表明肠道微生物与自身免疫病的发生之间具有莫大的联系,而具体到银屑病与肠道微生物之间的关系也并不清楚。针对这一问题,来自美国NIH的WanJun Chen课题组做了相关研究,结果发表在最近一期的nature communication 杂志上。


之前的研究发现:对小鼠的皮肤与耳部施加imiquimod(一类TLR-7拮抗剂)能够诱发类似人类银屑病的皮炎,并伴随一系列类似的症状,例如皮肤增厚,过度角质化,棘皮症等等。利用这一模型,作者观察了小鼠在接受抗生物药物治疗前后皮炎的变化情况。

首先,作者根据前人的试验方法对小鼠进行imiquimod刺激,并且观察到了明显的银屑病皮炎症状,细胞因子检测结果表明imiquimod的处理能够大幅提高表皮细胞中IL-1b,IL-17以及IL-22的表达。

之后,作者分别利用万古霉素与多粘菌素B清除成年小鼠肠道内的革兰氏阳性菌与革兰氏阴性菌,经过四周的抗生素饲喂之后再进行imiquimod的刺激。检测结果表明,接受抗生素处理的成年小鼠在接受imiquimod刺激之后皮肤的炎性症状相比于单纯的imiquimod刺激要明显下降,同时,作者发现在受到双重刺激的小鼠皮肤组织中的IL-17+ gamma delta T细胞的数量要明显低于对照组。而调节性T细胞的数量却有明显增多。另外,作者还通过表皮注射抗生素的方式清除皮肤组织中的微生物群落,得到了相似的结果。这些实验结果表明成年小鼠体内的肠道微生物的缺失有助于减缓银屑病的严重程度。

之后,作者们对刚出生的小鼠进行了相似的处理。意外的是,刚出生的小鼠在进行双重处理后银屑病的严重程度明显高于对照组,细胞水平的检测结果明刚出生小鼠在接受双重刺激后体内TCRgamma delta low+Vgamma4+IL-22+细胞数量明显高于单独的imiquimod刺激组,而其它类型的炎性细胞与调节性T细胞的数量并无显著差异,这与成年小鼠所展现的实验结果截然相反。

最后,作者通过微生物组学的手段证明在刚出生时期进行的抗生素处理能够显著改变小鼠肠道微生物的群落构成直至成年,他们认为这是导致刚出生小鼠在接受双重刺激之后银屑病恶化的关键原因。这一研究结果将银屑病这一自体免疫性疾病的发病机制与肠道微生物联系了起来。

原文出处:

Peter Zanvit, Joanne E.Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis.nat commun.2015
 

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    2017-09-11 1ddea163m76(暂无匿称)

    肠道菌群与银屑病.学习了

    0

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    2016-06-15 liye789132251
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    2016-03-11 贝儿

    看来排毒很重要

    0

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    2015-10-31 byzl

    那银屑病是不是可以通过清除肠道的有害菌治疗呢

    0

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    2016-04-13 liuli5079

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