A critical role of Dectin-1 in hypersensitivity pneumonitis
A critical role of Dectin-1 in hypersensitivity pneumonitis
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DOI：
10.1007/s00011-015-0910-1
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发表时间：
2016-03
影响因子：
6.7
通讯作者：
Mari Higashino-Kameda;T. Yabe-Wada;Shintaro Matsuba;K. Takeda;K. Anzawa;T. Mochizuki;K. Makimura;S. Saijo;Y. Iwakura;H. Toga;A. Nakamura
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文献类型：
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作者：
Mari Higashino-Kameda;T. Yabe-Wada;Shintaro Matsuba;K. Takeda;K. Anzawa;T. Mochizuki;K. Makimura;S. Saijo;Y. Iwakura;H. Toga;A. Nakamura
目的与设计超敏性肺炎（HP）是一种由于反复接触各种吸入性抗原（包括细菌和真菌）而引起的肺部疾病。尽管已知TLR是由细菌触发的HP产生所必需的，但真菌受体的意义仍不清楚。本研究的目的是探讨Dectin-1和Dectin-2是否参与了由真菌Trichosporon asahii（T.材料与方法我们研究了Dectin-Fc蛋白与T.用斑点杂交法测定。我们使用Dectin-1缺陷型（Dectin-1−/−）和Dectin-2−/−小鼠在HP模型中进行了组织学和流式细胞术分析。我们还研究了肺细胞中的Th 17/Th 1应答，并通过ELISA测量了来自骨髓来源的树突状细胞（BMDCs）的IL-17促进细胞因子IL-23。asahiithan Dectin-2. Dectin-1−/−小鼠几乎没有发生HP，而野生型小鼠和Dectin-2−/−小鼠都发生了类似的肺部疾病。Dectin-1缺陷减少中性粒细胞和单核细胞衍生的巨噬细胞的浸润，并抑制肺CD 4 +IL-17 A+细胞的扩增。IL-23 p19的产生在Dectin-1−/−BMDCs.ConclusionsThese data suggest Dectin-1 plays a critical role in the development of fungus-induced HP.
Objectives and designHypersensitivity pneumonitis (HP) is a pulmonary disease caused by repeated exposure to various aspiration antigens, including bacteria and fungi. Although TLRs are known to be required for the generation of HP triggered by bacteria, the significance of fungal receptors remains unclear. The present study aimed to investigate whether Dectin-1 and Dectin-2 contribute to the development of experimental HP triggered by the fungusTrichosporon asahii(T. asahii) that causes summer-type HP.Materials and methodsWe investigated the binding between Dectin-Fc protein andT. asahiiby a dot blot assay. We performed the histological and flow cytometric analysis in the HP model using Dectin-1-deficient (Dectin-1−/−) and Dectin-2−/−mice. We also investigated Th17/Th1 responses in lung cells, and measured an IL-17-promoting cytokine IL-23 from bone marrow-derived dendritic cells (BMDCs) by ELISA.ResultsDectin-1 bound more strongly toT. asahiithan Dectin-2. Dectin-1−/−mice barely developed HP, whereas both wild-type mice and Dectin-2−/−mice developed similar lung diseases. Dectin-1 deficiency decreased the infiltration of neutrophils and monocyte-derived macrophages and repressed the expansion of lung CD4+IL-17A+cells. The production of IL-23 p19 was reduced in Dectin-1−/−BMDCs.ConclusionsThese data suggested Dectin-1 plays a critical role in the development of fungus-induced HP.