Functional analysis of AIRE, a gene responsible for the hereditary type of autoimmune disease.
AIRE(一种导致遗传性自身免疫性疾病的基因)的功能分析。
基本信息
- 批准号:15390315
- 负责人:
- 金额:$ 8.83万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2004
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Autoimmune regulator (AIRE) gene mutation is responsible for the development of organ-specific autoimmune disease with monogenic autosomal recessive inheritance. Although Aire has been considered to regulate the elimination of autoreactive T cells through transcriptional control of tissue-specific antigens in thymic epithelial cells, other mechanisms of AlRE-dependent tolerance remain to be investigated. We have established Aire-deficient mice, and examined the mechanisms underlying the breakdown of self-tolerance. The production and/or function of immunoregulatory T cells were retained in the Aire-deficient mice. The mice developed Sjogren's syndrome-like pathologic changes in the exocrine organs, and this was associated with autoimmunity against a ubiquitous protein, a-fodrin. Remarkably, transcriptional expression of α-fodrin was retained in the Aire-deficient thymus. These results suggest that Aire regulates the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus, at least against this ubiquitous protein. Rather, Aire may regulate the processing and/or presentation of self-proteins so that the maturing T cells can recognize the self-antigens in a form capable of efficiently triggering autoreactive T cells. We also show that the first PHD (PHD1) of AIRE mediates E3 ligase activity. The significance of this finding was underscored by the fact that disease-causing missense mutations in the PHD1 (C311Y and P326Q) abolished its E3 ligase activity. These results add a novel enzymatic function for AIRE, and suggest an indispensable role of the ubiquitin-proteasome pathway in the establishment of self-tolerance in which AIRE is involved.
自身免疫性调节剂(AIRE)是用单基因的机器人特异性自身免疫性疾病的发展。仍在研究自我耐受性的分解。 。和/或自我蛋白质的表现,因此成熟的T细胞可以识别能够有效触发T-cells的形式的自我抗原。 p326q)废除了其E3连接酶的活性。
项目成果
期刊论文数量(16)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
AIRE functions as an E3 ubiquitin ligase.
- DOI:10.1084/jem.20031291
- 发表时间:2004-01-19
- 期刊:
- 影响因子:0
- 作者:Uchida D;Hatakeyama S;Matsushima A;Han H;Ishido S;Hotta H;Kudoh J;Shimizu N;Doucas V;Nakayama KI;Kuroda N;Matsumoto M
- 通讯作者:Matsumoto M
Kajiura F, et al.: "NF-κB-inducing kinaseestablishes self-tolerance in a thymic stroma dependent manner"Journal of Immunology. 172. 2067-2075 (2004)
Kajiura F 等人:“NF-κB 诱导激酶以胸腺基质依赖性方式建立自我耐受”《免疫学杂志》172. 2067-2075 (2004)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Uchida D, et al.: "AIRE functions as an E3 ubiquitin ligase"Journal of Experimental Medicine. 199. 167-172 (2004)
Uchida D 等人:“AIRE 具有 E3 泛素连接酶的功能”《实验医学杂志》。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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MATSUMOTO Mitsuru其他文献
MATSUMOTO Mitsuru的其他文献
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{{ truncateString('MATSUMOTO Mitsuru', 18)}}的其他基金
Elucidation of the pathogenesis of autoimmune diseases based on AIRE and development of novel therapies for the autoimmune diseases
基于AIRE阐明自身免疫性疾病发病机制并开发自身免疫性疾病新疗法
- 批准号:
19H03699 - 财政年份:2019
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Studies on the mechanisms underlying autoimmune ambivalence
自身免疫矛盾心理的机制研究
- 批准号:
18K19564 - 财政年份:2018
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Elucidation of the pathogenesis of autoimmune disease through the functional study of AIRE
通过AIRE的功能研究阐明自身免疫性疾病的发病机制
- 批准号:
16H05342 - 财政年份:2016
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Studies aiming the establishing self-tolerance for the cure of autoimmune disease
旨在建立自我耐受性以治愈自身免疫性疾病的研究
- 批准号:
25293223 - 财政年份:2013
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Role of Aire in the early development of zebrafish
Aire 在斑马鱼早期发育中的作用
- 批准号:
25670231 - 财政年份:2013
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Roles of AIRE in the development of early embryos and in the establishment of immunological self-tolerance
AIRE 在早期胚胎发育和免疫自我耐受建立中的作用
- 批准号:
22659097 - 财政年份:2010
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Transgenic mouse approaches to the pathogenesis of hereditary type of human autoimmune disease
转基因小鼠研究遗传型人类自身免疫性疾病的发病机制
- 批准号:
21390298 - 财政年份:2009
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Functional analysis ofAIRE, a gene responsible for the hereditary type of autoimmune disease
负责遗传型自身免疫性疾病的基因 AIRE 的功能分析
- 批准号:
17390291 - 财政年份:2005
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Functional analysis of the non-HLA genes within major histocompatibility complex (MHC) region with the use of gene-targeted mice
使用基因靶向小鼠对主要组织相容性复合体 (MHC) 区域内的非 HLA 基因进行功能分析
- 批准号:
11557013 - 财政年份:1999
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Role of lymphotoxin in lymphoid organogenesis and contact hypersensitivity.
淋巴毒素在淋巴器官发生和接触性超敏反应中的作用。
- 批准号:
09670478 - 财政年份:1997
- 资助金额:
$ 8.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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