Loss of kallikrein 5 expression exacerbates allergic skin inflammation including impairing filaggrin processing, promoting Th2 differentiation and inducing dysbiosis

mice demonstrated microbiome dysbiosis with enriched actinobacteria and reduced firmicutes in the skin, alteration in skin metabolites involved in the acetyl-CoA pathway and decreased expression of mature filaggrin monomers. Cutaneous application of Cis-Urocanic acid (cUCA) attenuated inflammatory responses highlighting barrier dysfunction as primary mechanism. We reveal an unappreciated role for KLK5 in inhibiting type 2 responses, acting through its roles in filaggrin processing and modulation of the skin microbiome and metabolome. Though KLK5 overactivation is known to contribute to several inflammatory skin disorders, our findings demonstrate that complete loss of KLK5 is also pathogenic in AD-like responses in mice.