DNA-dependent activator of IFN-regulatory factors (DAI) (DAI)

The DNA-dependent activator of IFN-regulatory factors (DAI), also known as ZBP1 or DLM-1, is a cytosolic DNA sensor that detects foreign DNAs, including B-DNA and Z-DNA conformations, through its N-terminal Zα, Zβ, and D3 DNA-binding domains to initiate innate immune responses. Upon binding, DAI undergoes conformational changes, activates IRF3 and NF-κB signaling pathways, and promotes type I interferon production and antiviral cytokine expression, while also associating with RIPK3 to trigger PANoptosis, an inflammatory programmed cell death. In immune cells like macrophages, DAI senses self-apoptotic DNA, driving M2b polarization via calcium signaling, which contributes to pathological inflammation. Elevated DAI expression is observed in systemic lupus erythematosus (SLE) patients and lupus models, where it exacerbates lupus nephritis by amplifying autoimmune responses. Knockdown or blockade of DAI ameliorates SLE symptoms by inhibiting macrophage activation and inflammation, positioning it as a potential therapeutic target, though no approved drugs currently target it.

Other names

ZBP1DLM-1Z-DNA-binding protein 1