Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells
NATURE COMMUNICATIONS
Authors: Zhao, Yinghua; Chu, Xiao; Chen, Jintong; Wang, Ying; Gao, Sujun; Jiang, Yuxue; Zhu, Xiaoqing; Tan, Guangyun; Zhao, Wenjie; Yi, Huanfa; Xu, Honglin; Ma, Xingzhe; Lu, Yong; Yi, Qing; Wang, Siqing
Abstract
Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF-kappa B signalling pathways, resulting in increased p50 and RelB nuclear translocation and TNFSF15 and OX40L expression. Furthermore, immunization of tumour-bearing mice with dectin-1-activated DCs induces potent antitumour response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9 cells and antitumour immunity and may have important clinical implications.
Association Analysis of Nonsyndromic Congenital Heart Disease and Tag Single Nucleotide Polymorphisms of TBX20 and Genes in the Ras-MAPK Pathway
GENETIC TESTING AND MOLECULAR BIOMARKERS
Authors: Luo, Zhiling; Shen, Yan; Chen, Wei; Ma, Xuejuan; Liu, Liping; Huang, Xiaoqin; Yang, Zhaoqing; Sun, Hao
Abstract
Aims: The present study was performed to determine whether there are variants in TBX20 and genes of the Ras-MAPK pathway associated with nonsyndromic congenital heart disease (ns-CHD). Materials and Methods: A total of 223 ns-CHD patients and 273 healthy controls from China were selected as study subjects to perform an association analysis using 22 tag single-nucleotide polymorphisms (tag SNPs) located either in one of three genes in the Ras-MAPK pathway (MAP2K2, BRAF, and RAF1) or the TBX20 gene that have previously been associated with syndromic congenital heart disease. Results: The results showed that none of these tag SNPs are associated with ns-CHD. Conclusions: The results suggested that these disease-causing genes, which were previously discovered in familial cases, might not be the major genetic factors causing the development of ns-CHD in Chinese.