Biased Generation and In Situ Activation of Lung Tissue-Resident Memory CD4 T Cells in the Pathogenesis of Allergic Asthma.
Biased Generation and In Situ Activation of Lung Tissue-Resident Memory CD4 T Cells in the Pathogenesis of Allergic Asthma.
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DOI：
10.4049/jimmunol.1700257
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发表时间：
2018-03-01
期刊：
影响因子：
--
通讯作者：
Farber DL
中科院分区：
文献类型：
--
作者：
Turner DL;Goldklang M;Cvetkovski F;Paik D;Trischler J;Barahona J;Cao M;Dave R;Tanna N;D'Armiento JM;Farber DL
哮喘是一种慢性炎症性疾病，由过敏原特异性的CD4T细胞介导，通过向肺内募集细胞效应物来促进肺部炎症。在感染和过敏原诱导后，肺T细胞的一个亚群可以作为组织驻留记忆T细胞(TRM)持续存在，尽管TRM的产生和在哮喘持续和发病机制中的作用尚不清楚。在这里，我们使用了一种慢性鼻腔暴露于屋尘螨提取物(HDM)的小鼠模型，分析了肺TRM是如何产生的，并在过敏性呼吸道疾病的持久性和发病机制中发挥了作用。我们证明，在急性HDM暴露期间，CD4+和CD8+T细胞都渗透到肺组织中；然而，在HDM停止给药后，只有CD4+TRM而不是CD8+TRM长期存在。肺中的CD4+TRM细胞定位于呼吸道周围，在过敏原再次暴露时迅速重新激活，并伴随着不依赖循环T细胞的呼吸道高反应性的快速诱导。肺内CD4+TRM的激活对HDM的攻击也伴随着肺内树突状细胞的募集和激活增加。我们的结果表明，肺内CD4+TRM可以维持变应原特异性致敏，并引导早期炎症信号促进快速肺病理，提示靶向肺内CD4+TRM可能在改善哮喘复发方面有治疗作用。
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells which promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRM) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. Here we used a mouse model of chronic exposure to intranasal house dust mite extract (HDM) to dissect how the lung TRM are generated and function in the persistence and pathogenesis of allergic airway disease. We demonstrate that both CD4+ and CD8+T cells infiltrate into the lung tissue during acute HDM exposure; however, only CD4+TRM, and not CD8+TRM persist longterm following cessation of HDM administration. Lung CD4+TRM cells are localized around airways and rapidly reactivated upon allergen re-exposure accompanied by the rapid induction of airway hyperresponsiveness independent of circulating T cells. Lung CD4+TRM activation to HDM challenge is also accompanied by increased recruitment and activation of dendritic cells in the lungs. Our results indicate that lung CD4+TRM can perpetuate allergen-specific sensitization and direct early inflammatory signals that promote rapid lung pathology, suggesting that targeting lung CD4+TRM could have therapeutic benefit in ameliorating recurrent asthma episodes.
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DOI：
10.1164/rccm.200308-1094oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Johnson, JR;Wiley, RE;Jordana, M
通讯作者：
Jordana, M
影响因子：
82.9
作者：
Park CO;Kupper TS
通讯作者：
Kupper TS
影响因子：
3.7
作者：
Olsson, N;Taub, DD;Nilsson, G
通讯作者：
Nilsson, G
DOI：
10.1126/science.1257530
发表时间：
2014-10-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iijima N;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
8
作者：
Christensen, D.;Mortensen, R.;Andersen, P.
通讯作者：
Andersen, P.