Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury.
Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury.
复制标题
DOI：
10.1002/emmm.201303236
复制
发表时间：
2014-03
影响因子：
11.1
通讯作者：
Fuchs, Serge Y.
中科院分区：
文献类型：
--
作者：
Bhattacharya, Sabyasachi;Katlinski, Kanstantsin V.;Reichert, Maximilian;Takano, Shigetsugu;Brice, Angela;Zhao, Bin;Yu, Qiujing;Zheng, Hui;Carbone, Christopher J.;Katlinskaya, Yuliya V.;Leu, N. Adrian;McCorkell, Kelly A.;Srinivasan, Satish;Girondo, Melanie;Rui, Hallgeir;May, Michael J.;Avadhani, Narayan G.;Rustgi, Anil K.;Fuchs, Serge Y.
1型干扰素通过结合同源受体(由IFNAR1/IFNAR2链组成)并诱导下游信号和基因表达来保护宿主免受病毒侵袭。然而，炎性刺激可以触发IFNAR1的泛素化和下调，从而在体外减弱干扰素的作用。这一自相矛盾的规定的意义尚不清楚。这里介绍的结果表明，无法在Ifnar1SA敲入小鼠中刺激IFNAR1泛素化使它们非常容易患上包括急性和慢性胰腺炎、自身免疫性和中毒性肝炎在内的多种炎症综合征。Ifnar1SA小鼠(或其接受骨髓的野生型动物)表现出持续的炎症组织免疫渗透、广泛的损伤和严重的组织再生不足。在野生型小鼠中，IFNAR1泛素化的药理刺激可以保护小鼠免受中毒性肝炎和暴发性全身性炎症的影响，但对Ifnar1SA小鼠没有保护作用。这些结果表明，触发IFNAR1泛素化以限制炎症诱导的组织损伤的内源性机制可以被有目的地模仿以获得治疗益处。学科类别免疫学；消化系统
Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1SA knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1SA mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1SA mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System
登录
查看更多内容
影响因子：
7.8
作者：
Kumar, K. G. Suresh;Barriere, Herve;Carbone, Christopher J.;Liu, Jianghuai;Swaminathan, Gayathri;Xu, Ping;Li, Ying;Baker, Darren P.;Peng, Junmin;Lukacs, Gergely L.;Fuchs, Serge Y.
通讯作者：
Fuchs, Serge Y.
影响因子：
8
作者：
HuangFu, W-C;Qian, J.;Liu, C.;Liu, J.;Lokshin, A. E.;Baker, D. P.;Rui, H.;Fuchs, S. Y.
通讯作者：
Fuchs, S. Y.
影响因子：
5.7
作者：
Fan, Hongkuan;Zingarelli, Basilia;Cook, James A.
通讯作者：
Cook, James A.
影响因子：
2.9
作者：
Kuehn, R;Lelkes, PI;Izbicki, JR
通讯作者：
Izbicki, JR
DOI：
10.1152/ajpgi.00078.2007
发表时间：
2007-06-01
影响因子：
4.5
作者：
Kubisch, Constanze H.;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.