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Cyld调节肠道炎症
作者:小柯机器人 发布时间:2020/5/19 13:17:46

美国西南医学中心K. Venuprasad研究组取得新进展。他们发现CyldNLRP6炎症小体的去泛素化主要调节肠道炎症。2020518日,《自然—免疫学》发表了这一成果。

他们证明了去泛素化酶Cyld通过去泛素化NLRP6,来防止结肠粘膜中过量的白介素18IL-18)产生。他们显示去泛素化抑制了NLRP6-ASC炎症小体复合物并调节了IL-18的成熟。小鼠的Cyld缺乏导致啮齿类柠檬酸杆菌感染后,活性IL-18水平升高和严重的结肠炎症。

此外,在溃疡性结肠炎患者中,活性IL-18的浓度与CYLD表达呈负相关。因此,他们已经确定了一种新的调节机制,该机制可抑制肠道炎症中的NLRP6-IL-18途径。

据介绍,炎症小体NLRP6在调节炎症和抵抗肠道微生物方面起着至关重要的作用。但是,抑制NLRP6功能以防止过度炎症的分子机制仍不清楚。

附:英文原文

Title: Deubiquitination of NLRP6 inflammasome by Cyld critically regulates intestinal inflammation

Author: Sandip Mukherjee, Ritesh Kumar, Elviche Tsakem Lenou, Venkatesha Basrur, Dimitris L. Kontoyiannis, Fotis Ioakeimidis, George Mosialos, Arianne L. Theiss, Richard A. Flavell, K. Venuprasad

Issue&Volume: 2020-05-18

Abstract: The inflammasome NLRP6 plays a crucial role in regulating inflammation and host defense against microorganisms in the intestine. However, the molecular mechanisms by which NLRP6 function is inhibited to prevent excessive inflammation remain unclear. Here, we demonstrate that the deubiquitinase Cyld prevents excessive interleukin 18 (IL-18) production in the colonic mucosa by deubiquitinating NLRP6. We show that deubiquitination inhibited the NLRP6–ASC inflammasome complex and regulated the maturation of IL-18. Cyld deficiency in mice resulted in elevated levels of active IL-18 and severe colonic inflammation following Citrobacter rodentium infection. Further, in patients with ulcerative colitis, the concentration of active IL-18 was inversely correlated with CYLD expression. Thus, we have identified a novel regulatory mechanism that inhibits the NLRP6–IL-18 pathway in intestinal inflammation.

DOI: 10.1038/s41590-020-0681-x

Source: https://www.nature.com/articles/s41590-020-0681-x

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex