The tetrapeptide sequence of IL-18 and IL-1β regulates their recruitment and activation by inflammatory caspases.

Inflammasomes are multiprotein signaling complexes that activate the innate immune system. Canonical inflammasomes recruit and activate caspase-1, which then cleaves and activates IL-1β and IL-18, as well as gasdermin D (GSDMD) to induce pyroptosis. In contrast, non-canonical inflammasomes, caspases-4/-5 (CASP4/5) in humans and caspase-11 (CASP11) in mice, are known to cleave GSDMD, but their role in direct processing of other substrates besides GSDMD has remained unknown.

The tetrapeptide sequence of IL-1β regulates its recruitment and activation by inflammatory caspases.

The mammalian innate immune system uses germline-encoded cytosolic pattern-recognition receptors (PRRs) to detect intracellular danger signals. At least six of these PRRs are known to form multiprotein complexes called inflammasomes which activate cysteine proteases known as caspases. Canonical inflammasomes recruit and activate caspase-1 (CASP1), which in turn cleaves and activates inflammatory cytokines such as IL-1β and IL-18, as well as the pore forming protein, gasdermin D (GSDMD), to induce pyroptotic cell death.

Altered Gut Microbiome and Fecal Immune Phenotype in Early Preterm Infants With Leaky Gut.

Intestinal barrier immaturity, or "leaky gut", is the proximate cause of susceptibility to necrotizing enterocolitis in preterm neonates. Exacerbated intestinal immune responses, gut microbiota dysbiosis, and heightened barrier injury are considered primary triggers of aberrant intestinal maturation in early life. Inordinate host immunity contributes to this process, but the precise elements remain largely uncharacterized, leaving a significant knowledge gap in the biological underpinnings of gut maturation.