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

Abstract Psoriasis is a chronic inflammatory skin disease that develops under the influence of the interleukin (IL)-23/Th17 axis and is characterized by intense inflammation and prominent epidermal hyperplasia. Here, we demonstrate that galectin-8, a β–galactoside-binding lectin, is upregulated in the epidermis of human psoriatic skin lesions, as well as a mouse model of psoriasis induced by intradermal IL-23 injections, and in IL-17A-treated keratinocytes. We show keratinocyte proliferation is less prominent in galectin-8-knockout mice following intradermal IL-23 treatment compared to wild type mice. In addition, we show that galectin-8 levels in keratinocytes are positively correlated with the ability of cells to proliferate, and that transition from mitosis into G1 phase is delayed in galectin-8-knockout HaCaT cells after cell cycle synchronization and release. We demonstrate by immunofluorescence staining and immunoblotting the presence of galectin-8 within the mitotic apparatus. We reveal by co-immunoprecipitation and mass spectrometry analysis that α-tubulin interacts with galectin-8 during mitosis. Finally, we show in the absence of galectin-8, pericentrin compactness is lessened and mitotic microtubule length is shortened, as demonstrated by immunofluorescence staining. We conclude that galectin-8 is upregulated in psoriasis and contributes to the hyperproliferation of keratinocytes by maintaining centrosome integrity during mitosis through interacting with α-tubulin.