Wu Renlan, Li Xingjie, Ma Ning, Jin Xiufeng, Yuan Xiefang, Qu Chen, Tang Hongmei, Liu Zhigang, Zhang Zongde
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Model Animal Research Center, Nanjing University, Nanjing 210061, China.
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, China.
iScience. 2020 Jul 24;23(7):101288. doi: 10.1016/j.isci.2020.101288. Epub 2020 Jun 20.
IgE and IgG1 production in the type 2 immune response is the characteristic feature of an allergic reaction. However, whether bacterial molecules modulate IgE and IgG1 production remains obscure. Here, we demonstrate that the bacterial quorum sensing molecules acyl homoserine lactones (AHLs) induce IgE and IgG1 production by activating the RARE (retinoic acid response element) response in dendritic cells (DCs) in vivo. DC-specific knockout of the retinoic acid transcriptional factor Rara diminished the AHL-stimulated type 2 immune response in vitro. AHLs altered DC phenotype, upregulated OX40L and IFN-I signature, and promoted T helper 2 cell differentiation in vitro. Finally, AHLs activated the RARE response by inhibiting AKT phosphorylation in vitro, as the AKT agonists IGF-1 and PDGF abolished the effect of AHLs on the RARE response. This study demonstrates a mechanism by which AHLs drive allergic airway inflammation through activating retinoic acid signaling in DCs.
2型免疫反应中IgE和IgG1的产生是过敏反应的特征。然而，细菌分子是否调节IgE和IgG1的产生仍不清楚。在这里，我们证明细菌群体感应分子酰基高丝氨酸内酯（AHLs）通过在体内激活树突状细胞（DCs）中的视黄酸反应元件（RARE）反应来诱导IgE和IgG1的产生。视黄酸转录因子Rara的DC特异性敲除减弱了体外AHL刺激的2型免疫反应。AHLs改变了DC表型，上调了OX40L和IFN-I特征，并在体外促进了辅助性T细胞2的分化。最后，AHLs在体外通过抑制AKT磷酸化来激活RARE反应，因为AKT激动剂IGF-1和PDGF消除了AHLs对RARE反应的影响。这项研究证明了一种机制，通过该机制AHLs通过激活DCs中的视黄酸信号传导来驱动过敏性气道炎症。
