Department of Dermatology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan.
Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
J Invest Dermatol. 2021 Mar;141(3):503-511.e9. doi: 10.1016/j.jid.2020.07.021. Epub 2020 Aug 15.
Psoriasis is a chronic inflammatory skin disease that develops under the influence of the IL-23/T helper 17 cell axis and is characterized by intense inflammation and prominent epidermal hyperplasia. In this study, we demonstrate that galectin-8, a β-galactoside‒binding lectin, is upregulated in the epidermis of human psoriatic skin lesions as well as in a mouse model of psoriasis induced by intradermal IL-23 injections and in IL-17A‒treated keratinocytes. We show that keratinocyte proliferation is less prominent in galectin-8‒knockout mice after intradermal IL-23 treatment than in wild-type mice. In addition, we show that galectin-8 levels in keratinocytes are positively correlated with the ability of the cells to proliferate and that transitioning 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 coimmunoprecipitation and mass spectrometry analysis that α-tubulin interacts with galectin-8 during mitosis. Finally, we show that 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.
银屑病是一种慢性炎症性皮肤病，在 IL-23/T 辅助性 17 细胞轴的影响下发展，其特征为强烈的炎症和明显的表皮增生。在这项研究中，我们证明了半乳糖凝集素-8（一种β-半乳糖苷结合凝集素）在人银屑病皮损的表皮中以及通过皮内注射 IL-23 诱导的小鼠银屑病模型和 IL-17A 处理的角质形成细胞中上调。我们表明，与野生型小鼠相比，在皮内注射 IL-23 后，半乳糖凝集素-8 敲除小鼠的角质形成细胞增殖不那么明显。此外，我们表明角质形成细胞中的半乳糖凝集素-8 水平与细胞增殖能力呈正相关，并且在细胞周期同步化和释放后，半乳糖凝集素-8 敲除 HaCaT 细胞从有丝分裂进入 G1 期的转变被延迟。我们通过免疫荧光染色和免疫印迹证明了有丝分裂器内存在半乳糖凝集素-8。我们通过共免疫沉淀和质谱分析揭示了在有丝分裂期间α-微管蛋白与半乳糖凝集素-8 相互作用。最后，我们表明在缺乏半乳糖凝集素-8 的情况下，中心体的致密性降低，有丝分裂微管长度缩短，如免疫荧光染色所示。我们得出结论，半乳糖凝集素-8 在银屑病中上调，并通过与α-微管蛋白相互作用在有丝分裂期间维持中心体完整性，从而促进角质形成细胞的过度增殖。
