Inflammasomes in respiratory diseases: from disease pathogenesis to drug development and use of multi-omics.

Inflammasomes are pivotal for the initiation and control of host inflammatory responses. This is particularly important in the respiratory system due to its direct exposure to noxious environmental and infectious stimuli, which can cause local inflammation, tissue damage and impaired function. Inflammasomes are activated by a variety of processes that result in a loss of cellular homeostasis, leading to the oligomerisation of specific innate immune sensors. Inflammasome complex formation then results in a form of programmed cell death known as pyroptosis and release of cleaved active pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, and the subsequent inflammatory cascade. While acute inflammasome activation can be protective in controlling infection, chronic inflammasome activation is detrimental and can lead to irreversible changes in the lung micro-environment such as chronic inflammation, emphysema, lung fibrosis and impaired gas exchange and lung function. In this review, we describe the role of inflammasomes in the pathogenesis of acute and chronic respiratory diseases, highlight currently available preclinical and clinically available therapies that regulate or inhibit inflammasome activation, and outline the use of multi-omics to identify novel inflammasome biomarkers and therapeutics.