The identification of key mechanisms and molecules involved in tertiary lymphoid organ formation in the central nervous system in MP4-induced experimental autoimmune encephalomyelitis

MP4诱导的实验性自身免疫性脑脊髓炎中枢神经系统三级淋巴器官形成的关键机制和分子的鉴定

• 批准号: 289784780
• 负责人: Professorin Dr. Stefanie Kürten
• 金额: --
• 依托单位: Anatomisches Institut
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/289784780?language=en
• 关键词: identification; key; mechanisms; molecules; involved

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) and supposed to be of autoimmune nature. While the role of T cells has been extensively studied, B cells have just begun to attract major attention. It was recently shown that B cells organize themselves into lymphoid follicle-like structures in the meninges of patients with secondary progressive MS and we have identified and functionally characterized similar tertiary lymphoid organs (TLO) in the B cell-dependent murine MP4-induced experimental autoimmune encephalomyelitis (EAE). The aim of this proposal is to identify key mechanisms and molecules involved in B cell aggregation and TLO formation in the cerebellum of MP4-immunized C57BL/6 mice. In Aim 1 RNA microarrays will be performed on non- and diffuse B cell infiltrates, B cell aggregates and TLO and the data will be compared to the expression profiles of CNS infiltrates in the B cell-independent myelin oligodendrocyte glycoprotein (MOG):35-55 model and of secondary lymphoid organs (SLO). The expression of designated markers will be confirmed by qRT-PCR and immunohistochemistry. In an attempt to perform an initial translation of the results to the setting of MS we will also search for the most promising molecules on MS brain sections that contain/do not contain B cell aggregates/follicles. Aim 2 will study the contribution of lymphoid tissue inducer (LTi) cells and podoplanin expressing TH17 cells to TLO formation in the MP4 model.

多发性硬化（MS）是一种慢性炎症性中枢神经系统疾病，被认为是自身免疫性疾病。虽然T细胞的作用已被广泛研究，但B细胞才刚刚开始引起人们的关注。最近的研究表明，B细胞在继发性进行性MS患者的脑膜中组织成淋巴滤泡样结构，我们在B细胞依赖性小鼠MP4诱导的实验性自身免疫性脑脊髓炎（EAE）中鉴定并功能表征了类似的三级淋巴器官（TLO）。该建议的目的是确定参与B细胞聚集和MP4免疫C57 BL/6小鼠小脑中TLO形成的关键机制和分子。在目标1中，将对非和弥漫性B细胞浸润、B细胞聚集体和TLO进行RNA微阵列，并将数据与CNS浸润在B细胞非依赖性髓鞘少突胶质细胞糖蛋白（MOG）：35-55模型和次级淋巴器官（SLO）中的表达谱进行比较。将通过qRT-PCR和免疫组织化学确认指定标志物的表达。在尝试将结果初步转化为MS设置时，我们还将在含有/不含有B细胞聚集体/滤泡的MS脑切片上搜索最有希望的分子。目的2研究MP4模型中淋巴组织诱导细胞（LTi）和表达podoplanin的TH 17细胞对TLO形成的作用。

项目成果

The enteric nervous system is a potential autoimmune target in multiple sclerosis

• DOI: 10.1007/s00401-017-1742-6
• 发表时间: 2017-06
• 期刊: Acta Neuropathologica
• 影响因子: 12.7
• 作者: Marie Wunsch;S. Jabari;B. Voussen;Michael Enders;S. Srinivasan;F. Cossais;T. Wedel;M. Boettner