Caspase-8 participates in two signaling complexes: the death inducing signaling complex (DISC) and the activation receptor induced signalosome (ARIS). In the former, death receptor stimulation results in caspase-8 activation and cleavage of downstream caspases, leading to the cell’s death. In the latter, immunoreceptor stimulation leads to caspase-8-dependent recruitment of the CARMA1 (Card11), Bcl10, MALT1 (CBM)-IκB kinase (IKK) complex and NF-κB activation. Caspase-8 deficiency state (CEDS) due to loss-of-function caspase-8 mutations causes an inherited disease with features of lymphoaccumulation, autoimmunity, and combined immunodeficiency.

Return to Human Immunological Diseases Unit