Francisco Juan Martínez Navarro¹, Francisco Javier Martínez Morcillo¹, María Azucena López Muñoz¹, Irene Pardo Sánchez¹, MARIA TERESA MARTINEZ MENCHON¹, Antonio Raul Corbalán Vélez¹, MARIA LUISA CAYUELA FUENTES², ANA BELEN PEREZ OLIVA¹, Diana García Moreno², Victoriano Mulero Méndez¹

(1) INMUNIDAD, INFLAMACIÓN Y CÁNCER, IMIB-Arrixaca, España
(2) CIRUGÍA DIGESTIVA, ENDOCRINA Y TRASPLANTE DE ÓRGANOS ABDOMINALES, IMIB-Arrixaca, España

Psoriasis is a skin inflammatory disorder that affects 3% of the human population. Although several therapies based on the neutralization of proinflammatory cytokines have been used with relative success, additional treatments are required.

In silico analysis of publicly available gene expression data of psoriasis lesional and non-lesional skin, together with the analysis of vitamin B6 metabolites in the sera of psoriasis patients before and after PUVA treatment, and functional studies in the zebrafish embryo/larval model.

The in silico analysis of gene expression data of psoriasis lesional skin and an analysis of vitamin B6 metabolites in the sera of psoriasis patients point to altered vitamin B6 metabolism at both local and systemic levels. Functional studies showed that vitamin B6 vitamers reduced skin neutrophil infiltration, oxidative stress and Nfkb activity in two zebrafish models of skin inflammation. Strikingly, inhibition of glycogen phosphorylase L (Pygl) and glucose-6-phosphate dehydrogenase (G6pd), two vitamin B6-regulated enzymes, alleviated oxidative-stress induced inflammation in zebrafish skin inflammation models.

Despite the central role of G6pd in antioxidant defenses, the results of the study demonstrate that glycogen stores and G6pd fuel NADPH oxidase to promote skin inflammation, revealing novel targets for the treatment of skin inflammatory disorders.