Andiappan AK

DOK3 promotes atopic dermatitis by enabling the phosphatase PP4C to inhibit the T cell signaling mediator CARD11

Atopic dermatitis (a type of eczema) is an itchy and painful inflammatory skin disorder of unknown cause, which is associated with decreased function of T cell signaling mediator CARD11 in some patients. Loh et al. found that a scaffolding protein may contribute to CARD11 repression and increased severity of atopic dermatitis symptoms in mice. The scaffolding protein DOK3, which was abundant in patient blood cells and bound strongly to patient-derived CARD11 variants, recruited the phosphatase PP4C to CARD11, functionally inactivating it and impairing T cell regulation. Reducing DOK3 abundance alleviated the symptoms in a mouse model of atopic dermatitis. Thus, the strength of the DOK3-CARD11 interaction may predict symptom severity in atopic dermatitis patients.