IκBζ is a key driver in the development of psoriasis

Significance Psoriasis is an inflammatory skin disease affecting 2–3% of the population. IL-17A plays a key role in psoriasis pathogenesis, and antibodies targeting IL-17A have recently been approved for psoriasis treatment. Here we demonstrate that IκBζ is a key protein for IL-17A–driven effects in psoriasis. IκBζ was demonstrated essential for both TNFα/IL-17A– and IL-17A–induced expression of a panel of psoriasis-associated proteins. Moreover, IκBζ expression was increased in psoriatic skin, and in two different psoriasis mouse models we showed that psoriasis development was completely absent in IκBζ-deficient mice, but inducible in IL-17A– and TNFα-deficient mice. Finally, local abrogation of IκBζ function in mouse skin abolished psoriasis development. These findings uncover a novel crucial regulatory mechanism involved in psoriasis development.