Caspase-8 triggers inflammatory signaling in multiple ways

Caspases are enzymes that control cell death. St. Jude scientists have found how an enzyme called caspase-8 helps cause inflammation.

“Caspase-8 plays a critical role in driving apoptotic cell death. The enzyme also blocks another form of cell death called necroptosis,” said Bart Tummers, PhD, Immunology. “Now we’ve found two ways that caspase-8 triggers inflammation.”  

The scientists studied a rare immune disorder linked to problems with cell death. Caspase-8 is involved in the process. This led to a study of the enzyme’s roles in cell death and inflammation.

The team found proteins that partner with caspase-8 and control the enzyme’s role in immune signaling. They also uncovered the importance of caspase-8’s ability to oligomerize, forming a complex made of multiple copies of the enzyme.

“Caspase-8 plays a role in inflammation that depends on its ability to oligomerize. This process was only observed when neither apoptosis nor necroptosis occurs,” said Douglas Green, PhD, Immunology chair.

Immunity published a report on this work.