NLRP3/NLRP1炎性小体调控Th17细胞功能和分化在甲状腺相关眼病发病机制中的研究

Thyroid-associated ophthalmopathy (TAO) has the highest incidence among orbital diseases, which results in visual impairment, craniofacial malformation and physical discomfort, with a great negative impact on patients’ quality of life and social psychological state. We first uncovered Th17 cell-mediated autoimmune reaction and fibrosis in the development of TAO. Due to the specific characteristics of orbital immunologic microenvironment, we found that infiltrating Th17 cells in retrobulbar tissues had obvious heterogeneity and the expression of NLRP3/NLRP1 was increased in Th17 cells in orbital tissues. It has been proved that inflammasome is closely related to the function of Th17 cells. This project will focus on the mechanism of NLRP3/NLRP1 molecular network in the regulation of Th17 cell function and differentiation, causing TAO attack. We will identify the phenotypic atlas of immune microenvironment of orbital connective tissues in TAO patients, discuss how NLRP3/NLRP1 molecular network influences the biological behavior of Th17 cells, discover novel therapeutic targets, and provide theoretical basis for precise treatment of TAO.

甲状腺相关眼病（thyroid-associated ophthalmolpathy，TAO）是发病率最高的眼眶病，导致视功能损伤、颅面畸形和身体不适，对患者的生活质量和社会心理状态有着极大的负面影响。我们首次揭示了Th17细胞介导的自身免疫反应和纤维化变性在TAO发生发展中的作用。由于眼眶局部免疫微环境的特殊性，我们发现浸润球后组织的Th17细胞存在明显的异质性，并且炎性小体NLRP3/NLRP1在眼眶组织中的Th17细胞内表达升高。业已证明，炎性小体和Th17细胞的功能密切相关，本项目将深入研究NLRP3/NLRP1分子网络调控Th17细胞功能与分化，影响TAO发病的作用机制。识别和鉴定TAO患者眼眶脂肪结缔组织中的免疫微环境表型图谱，探讨NLRP3/NLRP1分子网络如何影响Th17细胞的生物学行为，力争发现TAO新的治疗靶点，为其精准治疗提供理论依据和基础。