Regulation of antiviral immunity and autoimmune inflammation by the deubiquitinating enzyme USP15
去泛素化酶 USP15 调节抗病毒免疫和自身免疫炎症
基本信息
- 批准号:407678805
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2018
- 资助国家:德国
- 起止时间:2017-12-31 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Type I interferons (IFNs) are essential for antiviral immunity and often involved in autoimmune pathology. However, the regulation of IFN-induction and IFN-mediated signaling is not well understood. We and others have previously demonstrated that various deubiquitinating enzymes (DUBs) including USP18, USP25, and USP13 regulate antiviral immune responses and neuroinflammation through modulating IFN-induction and/or IFN-triggered signaling. In addition, we have identified USP15 being involved in IFN-signaling and induction. We have now generated a novel Usp15fl/fl mouse model to explore the physiological functions and the molecular mechanisms within the context of the whole organism. The focus of this proposal will be to analyze the role of USP15 in (I.) Antiviral immune responses and (II.) Autoimmune inflammatory diseases. To address this, mice either constitutively lacking USP15 or upon induced and cell-specific depletion will be virally infected as well as challenged by the inflammation models DSS induced colitis and experimental autoimmune encephalitis (EAE) and examined in comparison to control animals. The molecular role(s) of USP15 will be investigated with respect to the influence on pro-inflammatory signaling pathways, substrates, proteome composition and gene expression. Analysis of mouse models and molecular mechanisms will be complemented by the examination of samples from human patients to identify potential correlations and/or functional relationships with inflammatory diseases. We believe that this study will not only advance our understanding of immune and inflammatory responses, but also harbors the potential to define USP15 as a novel drug target for the treatment of interferonopathies, viral infections and/or inflammatory diseases.
I型干扰素(IFN)是抗病毒免疫所必需的,并且经常参与自身免疫病理学。然而,IFN-诱导和IFN-介导的信号转导的调节还没有很好地理解。我们和其他人先前已经证明,包括USP 18、USP 25和USP 13在内的各种去泛素化酶(DUB)通过调节IFN诱导和/或IFN触发的信号传导来调节抗病毒免疫应答和神经炎症。此外,我们已经确定USP 15参与IFN信号传导和诱导。我们现在已经产生了一种新的Usp 15 fl/fl小鼠模型,以探索整个生物体背景下的生理功能和分子机制。本提案的重点将是分析USP 15在(I.)抗病毒免疫应答和(II.)自身免疫炎性疾病。为了解决这一问题,组成型缺乏USP 15或在诱导和细胞特异性消耗后的小鼠将被病毒感染以及通过DSS诱导的结肠炎和实验性自身免疫性脑炎(EAE)的炎症模型攻击,并与对照动物进行比较。将研究USP 15对促炎信号通路、底物、蛋白质组组成和基因表达的影响的分子作用。对小鼠模型和分子机制的分析将通过对人类患者样本的检查来补充,以确定与炎症性疾病的潜在相关性和/或功能关系。我们相信,这项研究不仅将促进我们对免疫和炎症反应的理解,而且还具有将USP 15定义为治疗干扰素病,病毒感染和/或炎症性疾病的新型药物靶点的潜力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Privatdozent Dr. Klaus-Peter Knobeloch其他文献
Privatdozent Dr. Klaus-Peter Knobeloch的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Privatdozent Dr. Klaus-Peter Knobeloch', 18)}}的其他基金
Enzymatic and non-enzymatic functions of the SUMO isopeptidase USPL1 in vivo
SUMO 肽酶 USPL1 体内的酶促和非酶促功能
- 批准号:
398279577 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Research Grants
Function and regulation of the ISG15 specific isopeptidase USP18
ISG15 特异性肽酶 USP18 的功能和调节
- 批准号:
325088716 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Research Grants
Analysis of the ISG15 conjugation and deconjugation system in vivo
ISG15 体内缀合和解缀系统分析
- 批准号:
71963973 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Priority Programmes
Functional role of the ubiquitin specific protease 8 (USP8/UBPy) in T cells
泛素特异性蛋白酶 8 (USP8/UBPy) 在 T 细胞中的功能作用
- 批准号:
79091578 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Research Grants
Analyse der Funktion der Ubiquitin Isopeptidase UBPy (USP8) in vivo
泛素肽酶 UBPy (USP8) 体内功能分析
- 批准号:
31414656 - 财政年份:2006
- 资助金额:
-- - 项目类别:
Research Grants
Analysis of ISG15 effector functions in vivo
ISG15效应子体内功能分析
- 批准号:
5423693 - 财政年份:2004
- 资助金额:
-- - 项目类别:
Research Grants
相似国自然基金
SENP5调控磷酸化STAT2的SUMO修饰促进抗病毒天然免疫的机制研
究
- 批准号:
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
转录因子IRF3的泛素和SUMO修饰调节机制及其在抗病毒天然免疫中的功能
- 批准号:31130020
- 批准年份:2011
- 资助金额:315.0 万元
- 项目类别:重点项目
相似海外基金
Regulation and Manipulation of Oral Type III Interferon Responses by Porphyromonas gingivalis
牙龈卟啉单胞菌对口腔 III 型干扰素反应的调节和操纵
- 批准号:
10595198 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Negative regulation of human antiviral RNAi by PACT
PACT 对人类抗病毒 RNAi 的负调控
- 批准号:
10667112 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Regulation and Function of Oral Resident Memory T Cells
口腔驻留记忆 T 细胞的调节和功能
- 批准号:
10896496 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Regulation and Manipulation of Innate Immunity During HIV Infection
HIV 感染期间先天免疫的调节和操纵
- 批准号:
10874020 - 财政年份:2023
- 资助金额:
-- - 项目类别:
NON-CANONICAL MECHANISMS FOR INTERFERON-LAMBDA REGULATION OF SARS-COV-2 INFECTION
干扰素-Lambda 调节 SARS-COV-2 感染的非典型机制
- 批准号:
10574001 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Interferon regulation of gamma delta intraepithelial lymphocyte activation
干扰素调节γδ上皮内淋巴细胞活化
- 批准号:
10819812 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Regulation of the MAVS Signalosome by RNA and RNA-binding Proteins
RNA 和 RNA 结合蛋白对 MAVS 信号体的调节
- 批准号:
10640526 - 财政年份:2023
- 资助金额:
-- - 项目类别:
IL-17 regulation of type-1 immunity in chronic viral infection
IL-17 对慢性病毒感染中 1 型免疫的调节
- 批准号:
10641910 - 财政年份:2022
- 资助金额:
-- - 项目类别: