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T-bet induced age-associated B cells contribute to multiple sclerosis pathology and progression (R-9170)

In autoimmune diseases, the immune system aberrantly targets self-tissues, such as the central nervous system in multiple sclerosis (MS). B cells are important immune cells contributing to MS pathogenesis by the production of antibodies that mark self-antigens for immune mediated destruction, by stimulating T cell responses and by producing immunological mediators (cytokines). A proportion of MS patients have characteristics of an aged immune system. During aging, immune function decreases and age-associated B cells (ABCs) with an adverse function expand. Our research group recently reported increased frequencies of ABCs with pro-inflammatory characteristics in a proportion of MS patients. Although these ABCs could contribute to pathological processes in MS, details about their function in MS remain unknown. The aim of this project is to explore how expanded ABCs contribute to MS pathology and if their expansion is driven by the transcription factor T-bet. Therefore, the impact of increased ABCs on disease severity and progression is investigated. Next, expression of T-bet and its downstream regulators is measured in ABCs and the effect of T-bet induction on the function of ABCs is examined. The contribution of ABCs to disease progression in vivo is investigated by transferring isolated ABCs into a mouse model of MS. This study will clarify how ABCs contribute to harmful processes in MS patients, which provides better insights into MS pathogenesis.
Date:1 Oct 2018 →  30 Sep 2022