Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity.
Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity.
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DOI：
10.1016/j.jaci.2011.10.036
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Umetsu DT
中科院分区：
文献类型：
--
作者：
Kim HY;Chang YJ;Subramanian S;Lee HH;Albacker LA;Matangkasombut P;Savage PB;McKenzie AN;Smith DE;Rottman JB;DeKruyff RH;Umetsu DT
哮喘被认为是一种由Th 2细胞和获得性免疫介导的免疫性疾病。然而，临床和实验观察表明，其他途径可以调节哮喘，特别是在非过敏性哮喘形式中，例如与空气污染，压力，肥胖和感染相关的哮喘。我们的目标是了解可能导致气道高反应性（AHR）的非Th 2细胞依赖性条件，这是哮喘的主要特征。我们研究了实验性哮喘的小鼠模型，其中AHR是用糖脂抗原诱导的，糖脂抗原激活自然杀伤T（NKT）细胞。在该模型中，当小鼠用NKT细胞活化糖脂抗原治疗时，即使在没有常规CD 4 + T细胞的情况下，AHR也迅速发展。活化的NKT细胞直接诱导肺泡巨噬细胞产生IL-33，这反过来又激活NKT细胞以及天然辅助细胞，一种新描述的非T、非B先天淋巴细胞类型，以增加IL-13的产生。令人惊讶的是，这种糖脂诱导的AHR途径不仅需要IL-13，还需要IL-33及其受体ST 2，因为它被抗ST 2 mAb阻断，并且在ST 2 −/−小鼠中大大减少。当过继转移到IL-13−/−小鼠中时，野生型自然辅助细胞和NKT细胞都足以产生糖脂诱导的AHR。由于植物花粉，室内灰尘和一些细菌含有可以直接激活NKT细胞的糖脂，这些研究表明，AHR和哮喘可以通过涉及IL-33，天然辅助细胞和NKT细胞的先天免疫机制完全发展或大大增强。
Asthma has been considered an immunological disease mediated by Th2 cells and adaptive immunity. However, clinical and experimental observations suggest that additional pathways may regulate asthma, particularly in non-allergic forms of asthma, such as asthma associated with air pollution, stress, obesity and infection. Our goal was to understand Th2 cell-independent conditions which might lead to airway hyperreactivity (AHR), a cardinal feature of asthma. We examined a mouse model of experimental asthma, in which AHR was induced with glycolipid antigens, which activate natural killer T (NKT) cells. In this model, AHR developed rapidly when mice were treated with NKT cell-activating glycolipid antigens, even in the absence of conventional CD4+ T cells. The activated NKT cells directly induced alveolar macrophages to produce IL-33, which in turn activated NKT cells as well as natural helper cells, a newly described non-T, non-B, innate lymphoid cell type, to increase production of IL-13. Surprisingly, this glycolipid-induced AHR pathway required not only IL-13, but also IL-33 and its receptor, ST2, since it was blocked by an anti-ST2 mAb, and was greatly reduced in ST2−/− mice. When adoptively transferred into IL-13−/− mice, both wildtype natural helper cells and NKT cells were sufficient for the development of glycolipid induced AHR. Since plant pollens, house dust and some bacteria contain glycolipids that can directly activate NKT cells, these studies suggest that AHR and asthma can fully develop, or be greatly enhanced, through innate immune mechanisms, involving IL-33, natural helper cells and NKT cells.
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DOI：
10.4049/jimmunol.1003020
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kouzaki H;Iijima K;Kobayashi T;O'Grady SM;Kita H
通讯作者：
Kita H
CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
DOI：
10.1084/jem.20051166
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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DOI：
10.1016/j.jaci.2010.10.048
发表时间：
2011-02
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Huang YJ;Nelson CE;Brodie EL;Desantis TZ;Baek MS;Liu J;Woyke T;Allgaier M;Bristow J;Wiener-Kronish JP;Sutherland ER;King TS;Icitovic N;Martin RJ;Calhoun WJ;Castro M;Denlinger LC;Dimango E;Kraft M;Peters SP;Wasserman SI;Wechsler ME;Boushey HA;Lynch SV;National Heart, Lung, and Blood Institute's Asthma Clinical Research Network
通讯作者：
National Heart, Lung, and Blood Institute's Asthma Clinical Research Network
DOI：
10.1164/rccm.200702-323oc
发表时间：
2007-10-01
影响因子：
24.7
作者：
Johnston, Richard A.;Zhu, Ming;Shore, Stephanie A.
通讯作者：
Shore, Stephanie A.
影响因子：
15.9
作者：
Bedoret, Denis;Wallemacq, Hugues;Bureau, Fabrice
通讯作者：
Bureau, Fabrice