单核细胞参与Graves'病甲亢致病机制研究

Graves’病甲亢（GD）是一种常见的器官特异性自身免疫性疾病，临床表现复杂，疗程长，复发率高。既往研究发现单核细胞及其不同亚型参与多种自身免疫炎症反应，调控CD4+T细胞分化及功能；表观遗传学改变在自身免疫性疾病的发病、进展中具有重要作用，单核细胞可增加活性氧的生成对表观遗传学发挥作用。CD4+T细胞异常在GD自身抗体产生过程中起着桥梁作用。本课题组前期研究发现GD患者外周血单核细胞增多，各亚型比例改变，中间型细胞增多，且与TRAb水平显著正相关；在GD患者手术标本中发现甲状腺组织内单核细胞增多，但单核细胞及其不同亚型在GD中的作用机制尚不清楚。本课题组拟深入研究单核细胞及其不同亚型对T细胞分化和功能的作用及机制，探索单核细胞及其不同亚型对甲状腺细胞表观遗传学的影响。本项目预期研究结果将首次揭示单核细胞及其不同亚型参与GD的细胞和表观遗传学机制，为明确GD致病机制和治疗寻找新的方向。

Graves’ disease（GD）is a common organ specific autoimmune disorder with varied manifestations, long course and high recurrence rate. Monocyte subsets perturbation play prominent roles in autoimmune disease, regulating differentiation and function of CD4+T cells. Epigenetic modifications play important roles in the incidence and progression of GD. CD4+T cells are critical for autoantibody production in GD. Our preliminary study has found that monocytes increased in peripheral blood, intermediate monocytes increased and correlated with TRAb levels，however little is known about the pathogenesis of monocytes and its subsets in GD. According to the results of previous trials, we will demonstrate the contribution and mechanism of monocyte subsets in control of CD4+T cells development, and explore their influence on the epigenetic of thyroid cells. The expected results of this project will reveal for the first time that the impact of monocytes and monocyte subsets on GD, and provide a basis for understanding the pathogenesis network of GD and developing novel therapeutic strategy.