POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity.
POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity.
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POH1 去泛素化前白细胞介素 1 β 并限制炎症小体活性
DOI：
10.1038/s41467-018-06455-z
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发表时间：
2018-10-12
影响因子：
16.6
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Zhang L;Liu Y;Wang B;Xu G;Yang Z;Tang M;Ma A;Jing T;Xu X;Zhang X;Liu Y
炎性小体的激活对宿主防御入侵病原体是必不可少的，但也与各种形式的炎症性疾病有关。因此，控制炎性小体活动的过程对于避免过度的免疫反应和组织损伤非常重要。在这里，我们表明，去泛素酶POH1负向调节炎症小体激活所触发的免疫反应。巨噬细胞中POH1缺乏可增强成熟IL-1β的产生，而在炎性小体启动和Asc-caspase-1激活方面没有明显改变。在WT巨噬细胞中，POH1通过减少K63连接的多泛素链与前IL-1β相互作用并使其去泛素化，同时也降低了前IL-1β的切割效率。此外，在体内，髓系细胞特异性POH1的缺失加重了脂多糖诱导的全身炎症和明胶诱导的腹膜炎反应。因此，我们的研究表明，POH1介导的前IL-1β去泛素化是一个重要的调节事件，它抑制炎症反应，维持免疫平衡。炎性小体对于激活促炎细胞因子白介素1(IL-1β，IL-1β)起重要作用，从而保护机体免受病原体侵袭。在这里，作者证明了去泛素酶，POH1，减少了前IL-1β到其活性形式的转换，体内数据进一步暗示POH1在维持免疫动态平衡方面的作用。
Inflammasome activation is essential for host defence against invading pathogens, but is also involved in various forms of inflammatory diseases. The processes that control inflammasome activity are thus important for averting excessive immune responses and tissue damage. Here we show that the deubiquitinase POH1 negatively regulates the immune response triggered by inflammasome activation. POH1 deficiency in macrophages enhances mature IL-1β production without significant alterations in inflammasome priming and ASC-caspase-1 activation. In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1β by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1β cleavage. Furthermore, myeloid cell-specific deletion of POH1 aggravates lipopolysaccharide-induced systemic inflammation and alum-induced peritonitis inflammatory responses in vivo. Our study thereby reveals that POH1-mediated deubiquitination of pro-IL-1β is an important regulatory event that restrains inflammatory responses for the maintenance of immune homeostasis. The inflammasomes are important for activating the pro-inflammatory cytokine interleukin-β (IL-1β) for protection against pathogens. Here the authors show that a deubiquitinase, POH1, reduces the conversion of pro-IL-1β into its active form, with in vivo data further implicating a role of POH1 for maintaining immune homeostasis.
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影响因子：
23.9
作者：
Buckley, Shannon M.;Aranda-Orgilles, Beatriz;Strikoudis, Alexandros;Apostolou, Effie;Loizou, Evangelia;Moran-Crusio, Kelly;Farnsworth, Charles L.;Koller, Antonius A.;Dasgupta, Ramanuj;Silva, Jeffrey C.;Stadtfeld, Matthias;Hochedlinger, Konrad;Chen, Emily I.;Aifantis, Iannis
通讯作者：
Aifantis, Iannis
影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
影响因子：
--
作者：
Maytal-Kivity V;Reis N;Hofmann K;Glickman MH
通讯作者：
Glickman MH
影响因子：
16.6
作者：
Ratsimandresy RA;Chu LH;Khare S;de Almeida L;Gangopadhyay A;Indramohan M;Misharin AV;Greaves DR;Perlman H;Dorfleutner A;Stehlik C
通讯作者：
Stehlik C
影响因子：
32.4
作者：
Duong, Bao H.;Onizawa, Michio;Oses-Prieto, Juan A.;Advincula, Rommel;Burlingame, Alma;Malynn, Barbara A.;Ma, Averil
通讯作者：
Ma, Averil