A dominant negative tyrosine kinase 2 mutation abolishes interleukin-23 signalling and drives severe adult kerion caused by Trichophyton violaceum

We identified a heterozygous dominant negative TYK2 mutation (p.Y1080C) in a 74-year-old patient with severe, refractory kerion caused by Trichophyton violaceum. This mutation abolished IL-23/STAT3 signalling, impaired Th17 cell differentiation and led to absent S100A8 expression and futile neutrophilic inflammation in Tyk2 knockout mice. Our findings establish a nonredundant role for TYK2 in cutaneous defence against dermatophytes and raise caution for potential susceptibility to such infections in patients receiving TYK2-targeted therapies.