Inflammasome signaling and regulation of interleukin-1 family cytokines

Specific IL-1 family cytokines are initially expressed as inactive, cytosolic pro-forms. Chan and Schroder review inflammasome signaling and cell death decisions, mechanisms underpinning IL-1α, IL-1β, IL-18, and IL-37 maturation and release, and the functions of these cytokines in protective and pathological inflammation.
Specific IL-1 family cytokines are expressed by cells as cytosolic pro-forms that require cleavage for their activity and cellular release. IL-1β, IL-18, and IL-37 maturation and secretion is governed by inflammatory caspases within signaling platforms called inflammasomes. By inducing pyroptosis, inflammasomes can also drive the release of the alarmin IL-1α. Recent advances have transformed our mechanistic understanding of inflammasome signaling, cell death decisions, and cytokine activation and secretion. Here, we provide an updated view of inflammasome signaling; mechanisms underpinning IL-1α, IL-1β, IL-18, and IL-37 maturation and release; and the functions of these cytokines in protective and pathological inflammation.