Lung Natural Helper Cells Are a Critical Source of Th2 Cell-Type Cytokines in Protease Allergen-Induced Airway Inflammation
Lung Natural Helper Cells Are a Critical Source of Th2 Cell-Type Cytokines in Protease Allergen-Induced Airway Inflammation
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DOI：
10.1016/j.immuni.2011.12.020
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发表时间：
2012-03-23
期刊：
影响因子：
32.4
通讯作者：
Takei, Fumio
中科院分区：
文献类型：
--
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
肺中辅助性T细胞2（Th 2）细胞过度产生细胞因子被认为是哮喘的原因。在这里，我们报告说，先天淋巴细胞称为肺自然辅助（LNH）细胞是一个T细胞的非依赖性来源的Th 2细胞型细胞因子在蛋白酶过敏原治疗的肺。LNH（Lin（-）Sca-1（+）c-kit（+/lo）CD 25（+）CD 127（+））细胞在IL-33加IL-2、IL-7或胸腺基质淋巴细胞生成素（TSLP）刺激下产生大量IL-5和IL-13。鼻内给予蛋白酶过敏原木瓜蛋白酶可诱导野生型和Rag 1（-/-）小鼠肺中嗜酸性粒细胞浸润和粘液分泌过多，但在缺乏LNH细胞的Rag 2（-/-）Il 2 rg（-/-）小鼠中则不然。去除LNH细胞可抑制Rag 1（-/-）小鼠中木瓜蛋白酶诱导的气道炎症，而过继转移LNH细胞可使Rag 2（-/-）Il 2 rg（-/-）小鼠对木瓜蛋白酶产生反应。用木瓜蛋白酶处理肺外植体诱导基质细胞产生IL-33和TSLP以及LNH细胞产生IL-5和IL-13。因此，LNH细胞对于蛋白酶过敏原诱导的气道炎症至关重要。
Overproduction of cytokines by T helper 2 (Th2) cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) cells are a T cell-independent source of Th2 cell-type cytokines in protease allergen-treated lungs. LNH (Lin(-)Sca-1(+)c-kit(+/lo) CD25(+)CD127(+)) cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1(-/-) mice, but not in Rag2(-/-)Il2rg(-/-) mice that lack LNH cells. LNH cell depletion inhibited papain-induced airway inflammation in Rag1(-/-) mice whereas adoptive transfer of LNH cells enabled Rag2(-/-)Il2rg(-/-) mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma cells and IL-5 and IL-13 production by LNH cells. Thus, LNH cells are critical for protease allergen-induced airway inflammation.