T-cell immunoglobulin and mucin domain 1 deficiency eliminates airway hyperreactivity triggered by the recognition of airway cell death.
T-cell immunoglobulin and mucin domain 1 deficiency eliminates airway hyperreactivity triggered by the recognition of airway cell death.
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DOI：
10.1016/j.jaci.2013.03.025
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发表时间：
2013-08
影响因子：
14.2
通讯作者：
Umetsu, Dale T.
中科院分区：
文献类型：
--
作者：
Kim, Hye Young;Chang, Ya-Jen;Chuang, Ya-Ting;Lee, Hyun-Hee;Kasahara, David I.;Martin, Thomas;Hsu, Joyce T.;Savage, Paul B.;Shore, Stephanie A.;Freeman, Gordon J.;DeKruyff, Rosemarie H.;Umetsu, Dale T.
对哮喘的研究一直受到限制，因为对非过敏性环境暴露（如空气污染和感染）如何在肺部转化为炎症和喘息的理解不足。我们的目标是了解非过敏性哮喘导致气道高反应性（AHR）的机制，气道高反应性是哮喘的一个独立于适应性免疫的基本特征。我们研究了实验性哮喘的小鼠模型，其中AHR是由呼吸道合胞病毒（RSV）感染或臭氧暴露诱导的，使用TIM 1/HAVCR 1（一种重要的哮喘易感基因）缺陷的小鼠。TIM 1 −/−小鼠在感染RSV或反复暴露于臭氧（空气污染的主要成分）时不会发生气道疾病。另一方面，如前所述，TIM 1 −/−小鼠发生了过敏原诱导的实验性哮喘。RSV和臭氧诱导的途径被半胱天冬酶抑制剂治疗阻断，表明程序性细胞死亡和凋亡的绝对要求。TIM-1表达，但不是TIM-1缺陷，自然杀伤T（NKT）细胞响应凋亡气道上皮细胞分泌细胞因子，介导气道高反应性的发展。我们定义了一种新的途径，其中TIM-1，一种由凋亡细胞表达的磷脂酰丝氨酸受体，通过感知和响应受损和凋亡的气道上皮细胞来驱动哮喘的发展。
Studies of asthma have been limited by a poor understanding of how non-allergic environmental exposures such as air pollution and infection are translated in the lung into inflammation and wheezing. Our goal was to understand the mechanism of non-allergic asthma that lead to airway hyperreactivity (AHR), a cardinal feature of asthma independent of adaptive immunity. We examined mouse models of experimental asthma, in which AHR was induced by Respiratory Syncytial Virus (RSV) infection or ozone exposure, using mice deficient in TIM1/HAVCR1, an important asthma susceptibility gene. TIM1−/− mice failed to develop airways disease when infected with RSV or when repeatedly exposed to ozone, a major component of air pollution. On the other hand, the TIM1−/− mice developed allergen-induced experimental asthma, as previously shown. The RSV- and ozone-induced pathways were blocked by treatment with caspase inhibitors, indicating an absolute requirement for programmed cell death and apoptosis. TIM-1-expressing, but not TIM-1-deficient, natural killer T (NKT) cells responded to apoptotic airway epithelial cells by secreting cytokines, which mediated the development of airway hyperreactivity. We defined a novel pathway in which TIM-1, a receptor for phosphatidylserine expressed by apoptotic cells, drives the development of asthma by sensing and responding to injured and apoptotic airway epithelial cells.
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DOI：
10.4049/jimmunol.1001116
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lee HH;Meyer EH;Goya S;Pichavant M;Kim HY;Bu X;Umetsu SE;Jones JC;Savage PB;Iwakura Y;Casasnovas JM;Kaplan G;Freeman GJ;DeKruyff RH;Umetsu DT
通讯作者：
Umetsu DT
DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P
影响因子：
3.8
作者：
Deszcz, L;Gaudernak, E;Seipelt, J
通讯作者：
Seipelt, J
影响因子：
8.7
作者：
Freeman GJ;Casasnovas JM;Umetsu DT;DeKruyff RH
通讯作者：
DeKruyff RH
影响因子：
6.7
作者：
Jemielity S;Wang JJ;Chan YK;Ahmed AA;Li W;Monahan S;Bu X;Farzan M;Freeman GJ;Umetsu DT;Dekruyff RH;Choe H
通讯作者：
Choe H