上睑下垂
炎症体
细胞生物学
免疫系统
分泌物
受体
树突状细胞
模式识别受体
溶解循环
细胞因子
炎症
生物
免疫学
先天免疫系统
生物化学
病毒
作者
Lukas Hatscher,Christian Lehmann,Ariawan Purbojo,Constantin Onderka,Chunguang Liang,Arndt Hartmann,Robert Cesnjevar,Heiko Bruns,Olaf Groß,Falk Nimmerjahn,Ivana Ivanović‐Burmazović,Meik Kunz,Lukas Heger,Diana Dudziak
出处
期刊:Science Signaling
[American Association for the Advancement of Science (AAAS)]
日期:2021-04-27
卷期号:14 (680)
被引量:34
标识
DOI:10.1126/scisignal.abe1757
摘要
The detection of microorganisms and danger signals by pattern recognition receptors on dendritic cells (DCs) and the consequent formation of inflammasomes are pivotal for initiating protective immune responses. Although the activation of inflammasomes leading to secretion of the cytokine IL-1β is typically accompanied by pyroptosis (an inflammatory form of lytic programmed cell death), some cells can survive and exist in a state of hyperactivation. Here, we found that the conventional type 2 DC (cDC2) subset is the major human DC subset that is transcriptionally and functionally poised for inflammasome formation and response without pyroptosis. When cDC2 were stimulated with ligands that relatively weakly activated the inflammasome, the cells did not enter pyroptosis but instead secreted IL-12 family cytokines and IL-1β. These cytokines induced prominent T helper type 1 (TH1) and TH17 responses that were superior to those seen in response to Toll-like receptor (TLR) stimulation alone or to stronger, classical inflammasome ligands. These findings not only define the human cDC2 subpopulation as a prime target for the treatment of inflammasome-dependent inflammatory diseases but may also inform new approaches for adjuvant and vaccine development.
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