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

点击翻译按钮获取中文摘要

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.