Histone deacetylase 3 facilitates TNFα-mediated NF-κB activation through suppressing CTSB induced RIP1 degradation and is required for host defense against bacterial infection.

HDAC3 was required for protecting RIP1 from degrading by CTSB in macrophages. Decreased RIP1 in HDAC3 knockout macrophages impaired TNFα mediated NF-κB activation. Our studies uncovered important roles of HDAC3 in the regulation of cathepsin-mediated lysosomal degradation and RIP1-mediated inflammatory response in macrophages as well as in host defense against bacterial infection.