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The laboratory of Anne Bowcock showed in 2012 that rare inherited and de novo mutations in Card14 promote development of psoriasis. My group demonstrated in 2016 that psoriasis-associated Card14 mutations disrupt an intramolecular interaction in CARD14 and induce constitutive formation of a CARD14/BCL10/MALT1 complex, that triggers activation of NF-κB in keratinocytes. I will present our ongoing experiments to investigate how dysregulated CARD14 induces psoriasis. These have involved analyses of a new knock-in mouse strain in which the conditional expression of a psoriasis-associated CARD14 variant induces psoriasiform dermatitis and biochemical analyses of CARD14 signalling pathways in keratinocytes. These studies have significantly increased our understanding of the role of CARD14 in psoriasis aetiopathology and have potentially identified a novel therapeutic target for treatment of CARD14-dependent psoriasis.
