Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in Bim-/- mice

Abstract

Dysregulation of either the extrinsic or intrinsic apoptotic pathway can lead to various diseases including immune disorders and cancer. In addition to its role in the extrinsic apoptotic pathway, caspase-8 plays nonapoptotic functions and is essential for T cell homeostasis. The pro-apoptotic BH3-only Bcl-2 family member Bim is important for the intrinsic apoptotic pathway and its inactivation leads to autoimmunity that is further exacerbated by loss of function of the death receptor Fas. We report that inactivation of caspase-8 in T cells of Bim-/- mice restrained their autoimmunity and extended their life span. We show that, similar to caspase-8-/- T cells, Bim-/- T cells that also lack c..