The IκB kinase (IKK)-related kinases are central to the induction of the innate type I interferon (IFN) response [8]. A set of rare autoimmune disorders known as type I interferonopathies are caused by disturbance of the homeostatic control of induction, transmission, and resolution of the type I IFN-mediated immune response [7]. Therefore, members of this signaling pathway are subject to investigation as intervention points for pharmacological inhibition [5]. Initial investigations targeted IFN-I downstream signaling, including IFN-I proteins, IFNAR and the JAK/STAT signaling pathway. For example, sifalimumab (anti-IFN-α mAb), anifrolumab (anti-IFNAR1) and the JAK inhibitors ruxolitinib and tofacitinib, can all potentially tackle the effector function of dysregulated IFN by blocking downstream IFN-I signaling, but do not contribute to reducing the production of IFN. Upstream targeting of TBK1 and/or IKKε could be effective at blocking de novo IFN-I induction by a variety of stimuli. Small molecule kinase inhibitors of TBK1/IKKε already in development for cancer may expedite investigation for inflammatory diseases also [10].

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