Role of T cell subsets in the pathogenesis of autoimmune blistering disease (C04)

T 细胞亚群在自身免疫性水疱病发病机制中的作用 (C04)

• 批准号: 273675161
• 金额: --
• 依托单位: Klinik für Dermatologie
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/273675161?language=en
• 关键词: Role; cell; subsets; pathogenesis; autoimmune

Transfer of autoreactive CD4+ T cells from scurfy mice into T cell-deficient nude mice is sufficient to induce autoantibodies with reactivity to known autoantigens of autoimmune blistering diseases (AIBD). In this project we dissect the initial steps of AIBD-induction by analyzing the impact of different CD4+ T cell subsets for disease induction: We will transfer antigen-specific helper CD4+ T cells, as well as follicular helper T cells (Tfh) from scurfy mice to nude mice and test for induction of autoantibodies as well as clinical signs for AIBD. We will furthermore use this AIBD-model in a therapeutic setting in co-transfer experiments with different types of Treg (iTreg and nTreg). Finally, we will test one newly identified scurfy-derived pathogenic autoantibody for pathogenicity in humans by testing its blister-inducing capacity in human 3D skin models. In summary, these experiments will shed light on the role of various subtypes of CD4+ T cells in the induction of B cell-mediated autoimmune disease and the therapeutic potential of various subtypes of Treg.

将自身反应性CD4+ T细胞从皮屑小鼠转移到T细胞缺陷的裸鼠中足以诱导对自身免疫性水疱病（AIBD）的已知自身抗原具有反应性的自身抗体。在这个项目中，我们通过分析不同的CD4+ T细胞亚群对疾病诱导的影响来剖析AIBD诱导的初始步骤：我们将抗原特异性辅助性CD4+ T细胞以及滤泡辅助性T细胞（Tfh）从皮屑小鼠转移到裸鼠，并测试自身抗体的诱导以及AIBD的临床体征。我们还将在治疗环境中使用这种AIBD模型，进行不同类型Treg（iTreg和nTreg）的共转移实验。最后，我们将测试一个新发现的皮屑来源的致病性自身抗体在人类的致病性，通过测试其在人类3D皮肤模型中的水泡诱导能力。总之，这些实验将阐明CD4+ T细胞的各种亚型在诱导B细胞介导的自身免疫性疾病中的作用以及Treg的各种亚型的治疗潜力。