Centre International de Recherche en Infectiologie (CIRI), Univ Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France.
Int J Mol Sci. 2020 Oct 29;21(21):8087. doi: 10.3390/ijms21218087.
Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their activity is tightly regulated at the transcriptional and post-transcriptional levels. In this review, we present the transcriptional regulation of inflammasome genes from sensors (e.g., NLRP3) to substrates (e.g., IL-1β). Lineage-determining transcription factors shape inflammasome responses in different cell types with profound consequences on the responsiveness to inflammasome-activating stimuli. Pro-inflammatory signals (sterile or microbial) have a key transcriptional impact on inflammasome genes, which is largely mediated by NF-κB and that translates into higher antimicrobial immune responses. Furthermore, diverse intrinsic (e.g., circadian clock, metabolites) or extrinsic (e.g., xenobiotics) signals are integrated by signal-dependent transcription factors and chromatin structure changes to modulate transcriptionally inflammasome responses. Finally, anti-inflammatory signals (e.g., IL-10) counterbalance inflammasome genes induction to limit deleterious inflammation. Transcriptional regulations thus appear as the first line of inflammasome regulation to raise the defense level in front of stress and infections but also to limit excessive or chronic inflammation.
炎症小体是具有强大炎症活性的多分子复合物。因此，它们的活性在转录和转录后水平受到严格调节。在这篇综述中，我们介绍了从传感器（例如 NLRP3）到底物（例如 IL-1β）的炎症小体基因的转录调节。谱系决定转录因子在不同细胞类型中塑造炎症小体反应，对炎症小体激活刺激的反应有深远的影响。促炎信号（无菌或微生物）对炎症小体基因具有关键的转录影响，主要由 NF-κB 介导，并转化为更高的抗菌免疫反应。此外，各种内在（例如昼夜节律钟、代谢物）或外在（例如外源性物质）信号通过信号依赖性转录因子和染色质结构变化进行整合，以调节转录炎症小体反应。最后，抗炎信号（例如 IL-10）抵消炎症小体基因的诱导，以限制有害炎症。因此，转录调节似乎是炎症小体调节的第一道防线，可在应激和感染面前提高防御水平，但也可限制过度或慢性炎症。
