TANK-binding kinase 1 (TBK1): unexpected cell type-specific immune regulation beyond antiviral type I interferon signaling

Recognition of viral nucleic acids by multiple pattern-recognition receptors converges on TANK-binding kinase 1 (TBK1) to initiate type I interferon responses and antiviral immunity. While this canonical role is well established, recent studies using genetic ablation and pharmacological inhibition have reframed TBK1 as a context-dependent regulator of both innate and adaptive immunity across distinct cell lineages. Here, we review emerging cell-type-specific functions of TBK1 that extend beyond classical interferon signaling, repositioning it as a central coordinator of immune cell survival, differentiation, and effector function. We further discuss how pathways that signal through TBK1 may, thus, contribute to vaccine adjuvanticity, emphasizing this kinase as a potential target for vaccine-induced immunity. Finally, we outline how TBK1-dependent pathways may be harnessed for the design of next-generation vaccines.