Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s
Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s
复制标题
Dectin-2 通过激活 cDC2 促进屋尘螨偏向 Th2 反应
DOI：
10.1016/j.cellimm.2022.104558
复制
发表时间：
2022
影响因子：
4.3
通讯作者：
Chong Bai
中科院分区：
文献类型：
--
作者：
Yulan Qu;Xiaotian Ma;Jiewen Deng;Yan Shang;Kun Shang;Xinyu Wang;Zhenhong Guo;Chong Bai
Dectin-2（基因符号Clec 4 n）在屋尘螨（HDM）诱导的Th 2免疫应答中的作用及其确切机制仍存在争议。在本研究中，我们阐明了Clec 4 n-/-小鼠在HDM攻击后具有降低的Th 2免疫应答，这可能归因于Clec 4 n-/-小鼠肺中的2型常规树突状细胞（cDC 2s）显著减少，因为Clec 4 n-/-小鼠在攻击后肺中的cDC 2s诱导Th 2应答的能力降低，同时IL-4/IL-13的产生减少。进一步体外实验显示，HDM刺激后Clec 4 n-/--BMDCs的活化明显降低，同时伴有Syk-NF-κB和Syk-JNK信号通路的活化降低。哮喘患者外周血单个核细胞中Dectin-2的表达显著高于健康对照组。综上所述，这些结果表明，Dectin-2可以促进肺中cDC 2s的活化，从而极化Th 2免疫应答，概述了哮喘发展的新机制。
The role of Dectin-2 (gene symbol, Clec4n) in house dust mite (HDM) induced Th2 immune response and the exact mechanism remains controversial. In this study, we illustrated that, Clec4n-/- mice had decreased Th2 immune response following HDM challenge, which may ascribe to dramatically reduced type 2 conventional dendritic cells (cDC2s) in lung of Clec4n-/- mice, as cDC2s from lung of Clec4n-/- mice after challenging had less ability to induce Th2 response with decreased production of IL-4/IL-13. Further in vitro experiments showed the activation of Clec4n-/--BMDCs significantly decreased after HDM stimulation accompanied with decreased activation of Syk-NF-κB and Syk-JNK signal pathway. Importantly, Dectin-2 expression in PBMCs from asthmatic patients was significantly higher than that in healthy controls. Taken together, these results demonstrated that Dectin-2 could promote cDC2s activation in lung, which polarizes Th2 immune response outlining a novel mechanism of asthma development.