The tetrapeptide sequence of IL-18 and IL-1ß 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-1ß 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. Here, we show that CASP4/5 but not CASP11 can directly cleave and activate IL-18. However, CASP4/5/11 can all cleave IL-1ß to generate a 27-kDa fragment that deactivates IL-1ß signaling. Mechanistically, we demonstrate that the sequence identity of the tetrapeptide sequence adjacent to the caspase cleavage site regulates IL-18 and IL-1ß recruitment and activation. Altogether, we have identified new substrates of the non-canonical inflammasomes and reveal key mechanistic details regulating inflammation that may aid in developing new therapeutics for immune-related disorders.

Mechanisms of identity and gender decisions to faces: who rocked in 1986?

Two experiments are reported in which participants made familiarity decisions (Is this face familiar or not?) or gender decisions (Is this face male or female?) to the same sets of faces presented as whole faces or as internal features only. The experimental items on which the analysis was performed were famous and unfamiliar male faces that differed on rated masculinity. The famous faces also differed on age of acquisition (AoA). The experimental male faces were combined with an equal number of famous and unfamiliar female faces for presentation to participants. In experiment 1 we found faster and more accurate familiarity decisions to whole male faces than to internal features; also an interaction between AoA and masculinity such that familiarity decisions were both faster and more accurate to high- than to low-masculinity faces when those faces were late-acquired, but not when they were early-acquired. In experiment 2 we found the same benefit for whole faces over internal features and the same interaction between AoA and masculinity in gender decisions. The similarity between the effects of AoA and masculinity in familiarity and gender decisions is more readily accounted for by models of face processing which posit a close relationship between gender and identity processing than by models which maintain that those aspects of face perception are dealt with by quite separate processing streams. We propose that gender decisions, like familiarity decisions, are semantic judgments (rather than judgments based on the analysis of the surface features of faces), and that the shared basis of the two forms of decision explains why they show similar influences of AoA and masculinity.