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. 2020 Jan 9;100(3):983–1017. doi: 10.1152/physrev.00023.2019

FIGURE 3.

FIGURE 3.

“Inflammasome” linked interleukin (IL)-1β, IL-18, and IL-33 pathways in relation to downstream pathway activation and cellular responses. Both genetic and transcriptomic studies have strongly supported involvement of these cytokines in asthma phenotypes. These pathways are all activated by danger signals/receptors, with responses likely dependent on initiating signal, cell type, and perhaps genetic factors. IL-1β activation, through a classical inflammasome process, leads to broad activation of many cell types, generally linked to neutrophilic inflammation, perhaps through interferon (IFN)-γ or IL-17 pathways. Genetically associated IL-33 activation, arising from epithelial damage and augmented by inflammatory cell protease activity, stimulates ILC2 cells and mast cells/basophils to generate type 2 cytokines increasing type 2 immune responses. IL-18, strongly linked genetically with asthma through IL-18R1, can augment either type 1 or type 2 immune responses depending on the presence of IL-12. Interestingly, all 3 receptor pathways signal through MyD88, NF-κB, and Jun kinase (JNK) pathways. IL18RAP, IL-18 receptor activating protein; IL-18BP, IL-18 binding protein; sST2, soluble ST2/IL1RL1.