抗Gal3抗体通过NLRP3/Caspase-1/IL-1β通路介导系统性红斑狼疮皮肤血管炎的机制研究

血管炎是系统性红斑狼疮（SLE）不同组织器官临床表现的共同组织病理基础之一。我们前期研究发现抗galectin-3(Gal3)抗体引起皮肤血管炎，但是其具体机制还不清楚。组织病理显示受损血管周围局部组织内IL-1β显著升高；抗Gal3抗体促进人脐静脉内皮细胞(HUVEC)表达IL-1β，提示IL-1β升高与抗Gal3抗体引起的SLE皮肤血管炎有关。NLRP3炎症小体通过催化、剪切pro-caspase-1、pro-IL-1β成为活性caspase-1、IL-1β而在多种自身免疫性疾病中发挥重要作用。由此我们推测：抗Gal3抗体与血管内皮细胞Gal-3蛋白结合后活化NLRP3炎症小体，通过依次剪切生成caspase-1、IL-1β而促进内皮细胞坏死以及局部炎症微环境的形成，引起SLE皮肤血管炎。通过该项目的实施明确抗Gal3抗体引起皮肤血管炎的局部免疫学机制，为血管炎外用药物研发提供新靶点。

Vasculitis is one of the essential pathological disorders that lead to the various clinical manifestations of organs and tissues. Our previous research demonstrated that anti-gaelcitin-3 antibody induced cutaneous vasculitis by intracutaneous injection. However, the mechanism remains to be elucidated. Our preliminary data showed that IL-1β was significantly increased in the inflammatory area around the damaged blood vessels, and that the expression of IL-1β in HUVEC was greatly upregulated after incubation with anti-galectin-3 antibody, indicative a strong association of IL-1β with vasculitis induced by anti-galectin-3 antibody. NLRP3 inflammasome was involved in a serious of autoimmune diseases by splicing pro-caspase-1、pro-IL-1β into active caspase-1 and IL-1β after activated by stimuli. Considering these findings, we hypothesis that: anti-galectin-3 antibody combines with galectin-3 on endothelial cell surface, activates NLRP3 inflammasome which subsequently slices and activates caspase-1 and IL-1β. Caspase-1 directly damages endothelial cells, while IL-1β facilitates the development of local inflammation, which eventually results cutaneous vasculitis. This findings reveal the mechanism of galectin-3 antibody induced vasculitis and benefit the future research in finding new topical medicine for vasculitis.