我们前期研究发现巨噬细胞过度极化在自身免疫甲状腺炎中有重要作用，高碘不仅可以激活巨噬细胞，还可促进其M1型极化；我们还发现高碘在诱导巨噬细胞极化时可以促进m6A去甲基化酶ALKBH5的表达水平。已知碘过量是自身免疫甲状腺炎主要的危险因素，但其致病的分子机制尚不明确。因此，我们提出以下假说：碘过量可以促进巨噬细胞中m6A去甲基化酶ALKBH5的表达，继而特异性改变某些关键分子mRNA的m6A修饰水平及功能，促进巨噬细胞M1型极化并最终触发自身免疫甲状腺炎的发生。为了验证这一假说，我们拟采用临床研究、体外细胞培养和动物疾病模型，综合运用流式细胞术、RNA干扰、高通量测序和分子免疫学等实验方法，深入研究ALKBH5在碘过量致自身免疫甲状腺炎中的作用及具体分子机制。本研究将有助于深入阐述自身免疫甲状腺炎的发病机制，为其防治提供新的干预靶点。

Our previous studies found that macrophages play crucial roles in autoimmune thyroiditis and that iodine can promote macrophage polarization. Additionally, iodine can increase the expression of ALKBH5 during its induction of macrophage polarization. As is known, iodine excess is a major risk factor for autoimmune thyroiditis. The molecular mechanisms of iodine-induced thyroiditis are not well defined so far. To further explore the pathogenesis of autoimmune thyroiditis, we hypothesize that iodine can promote macrophage polarization by increasing ALKBH5 expression and regulating the mRNA methylation modifications of some key genes, thus exerting a crucial effect on the pathogenesis of autoimmune thyroiditis. To test this hypothesis, we will carry out clinical research, in-vitro experiments and in-vivo experiments through using a variety of techniques, such as flow cytometry, high-throughput sequencing, systems biology and molecular immunology, to study the regulatory role of ALKBH5 in iodine-induced thyroiditis and its relevant molecular mechanisms. Our study will shed novel insights into the mechanisms of autoimmune thyroiditis, and hopefully provide novel intervention targets for the prevention and treatment of the disease.