Epidermal hyperplasia is a characteristic histological feature in psoriasis, a chronic inflammatory skin disease of IL-23/IL-17A axis. Metabolically, proliferating cells require glucose uptake through glucose transporters. Indeed, keratinocytes in psoriasis lesions exhibit increased expression of Glut1, one of the most widely expressed glucose transporters. In addition, Glut1-deficient mice show impaired epidermal hyperplasia in mouse psoriasis models, suggesting that glucose metabolism through Glut1 is essential for epidermal hyperplasia in psoriasis. However, it remains unclear whether increased glucose metabolism in keratinocytes in psoriasis lesions returns to physiologically normal levels after treatments, such as biologics. To examine this, we performed an immunohistochemical analysis of Glut1 expression in psoriasis lesions before and four weeks after the treatment with secukinumab, an anti-IL-17A antibody (n = 6). Epidermal hyperplasia with increased Ki67 expression observed before treatment was markedly diminished after treatment. Before treatment, the expression levels of Glut1 were significantly upregulated in psoriasis lesions compared with the healthy skin in normal controls (n = 8), consistent with the previous reports. However, the expression levels were significantly decreased after treatment and were similar to those in healthy skin and non-lesional skin of psoriasis patients. The mRNA expression analysis using a public database set revealed that the expression of GLUT1 in psoriasis lesions was significantly down-regulated after ixekizumab treatment, another IL-17A antibody (n = 5). These results suggest that blockade of IL-17A pathyways reverses the increased glucose metabolism in keratinocytes and may reduce epidermal hyperplasia in psoriasis.

ESDR366 - Blockade of IL-17A pathway downregulates increased Glut1 expression in keratinocytes in psoriasis lesions and may reduce epidermal hyperplasia in psoriasis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.