Galectin-8 is upregulated in psoriasis and promotes IL-17A-induced keratinocyte proliferation by modulating mitosis

Psoriasis is a chronic inflammatory skin disease developed under the influence of the IL-23/Th17 axis and characterized by intense inflammation, as well as prominent epidermal hyperplasia. Here, we demonstrated that expression of galectin-8, a galactoside-binding lectin, was upregulated in the epidermis of human psoriatic skin lesions and the IL-23-induced mouse model. Meanwhile, galectin-8 knocked out mice showed a less prominent keratinocyte proliferation after intradermal IL-23 treatment. We also showed that IL-17A induced galectin-8 expression in human immortalized keratinocytes, HaCaT cells, and primary human keratinocytes, HEKn cells. In addition, we found that galectin-8 levels in keratinocytes were positively correlated with the proliferation ability of the cells. Furthermore, galectin-8 knocked out HaCaT cells showed a delay in transition from mitosis into G1 phase after cell cycle synchronization and release. The localization of galectin-8 within the mitotic apparatus was demonstrated by immunofluorescence staining and immunoblotting. Alpha-tubulin was one of the interacting proteins of galectin-8 during mitosis, as identified by co-immunoprecipitation and mass spectrometry analysis. In the absence of galectin-8, pericentrin compactness and mitotic tubule length were impaired as demonstrated by immunofluorescence staining. We conclude galectin-8 is upregulated in psoriasis and contributes to the hyperproliferation of keratinocytes by regulating mitosis through interacting with α-tubulin.