权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Ablation of Mina53 in mice reduces allergic response in the airways

小鼠中 Mina53 的消融可减少呼吸道过敏反应

基本信息

批准号：
21570204
负责人：
TSUNEOKA Makoto
金额：
$ 3.08万
依托单位：
Takasaki University of Health and Welfare
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

Asthma is a highly prevalent chronic respiratory disease affecting 300 million people world-wide. Allergic asthma is the most common form of asthma, a Th2-biased disease, and triggered by inhaling allergens such as house dust mites(HDM). In addition to the environmental factors, genetic factors are also involved in asthma. However, the interaction of these factors is complex and not fully understood. It was recently reported that Mina53 was a necessary and sufficient dose-dependent IL-4-specific 'repressor' in naive helper T cells, using an ex vivo system of Th2-differentiation from naive helper T cells(Nat Immunol. 2009 ; 10 : 872-9). However, there have been no experiments investigating the role of Mina53 in the Th2-bias in vivo in animals. While it had been reported that Mina53(myc-induced nuclear antigen with a 53 kDa molecular mass ; also known as mina) is associated with tumorigenesis, it was not clear what role Mina53 plays in non-neoplastic tissues. To directly address the functions of Mina53 in a normal body, we created mina53-deficient mice. While both male and female mina53-deficient mice grew to adulthood and were fertile, we found that Mina53 functions as an 'activator' in the allergic response, in asthma, possibly through controlling IL-4 production. We also analyzed the effect of succinate on ribosome biogenesis, and found that succinate inhibited another JmjC protein KDM2A to increase the rDNA transcription.

哮喘是一种非常流行的慢性呼吸道疾病，影响全球 3 亿人。过敏性哮喘是最常见的哮喘形式，是一种 Th2 偏向性疾病，由吸入屋尘螨 (HDM) 等过敏原引发。除了环境因素外，遗传因素也与哮喘有关。然而，这些因素的相互作用很复杂并且尚未完全了解。最近据报道，使用从幼稚辅助 T 细胞进行 Th2 分化的离体系统，Mina53 是幼稚辅助 T 细胞中必要且充分的剂量依赖性 IL-4 特异性“阻遏物”(Nat Nutritionol. 2009; 10: 872-9)。然而，还没有实验研究 Mina53 在动物体内 Th2 偏向中的作用。虽然已有报道Mina53（分子量为53 kDa的myc诱导的核抗原；也称为mina）与肿瘤发生有关，但尚不清楚Mina53在非肿瘤组织中发挥什么作用。为了直接解决 Mina53 在正常体内的功能，我们创建了 mina53 缺陷小鼠。虽然 mina53 缺陷的雄性和雌性小鼠都能生长到成年并具有生育能力，但我们发现 Mina53 可能通过控制 IL-4 的产生而在过敏反应和哮喘中发挥“激活剂”作用。我们还分析了琥珀酸对核糖体生物发生的影响，发现琥珀酸抑制另一种JmjC蛋白KDM2A以增加rDNA转录。