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• W1999712988 abstract "During the last decade, several defects in self-tolerance have been identified in multiple sclerosis. Dysfunction in central tolerance leads to the thymic output of antigen-specific T cells with T cell receptor alterations favouring autoimmune reactions. In addition, premature thymic involution results in a reduced export of naïve regulatory T cells, the fully suppressive clone. Alterations in peripheral tolerance concern costimulatory molecules as well as transcriptional and epigenetic mechanisms. Recent data underline the key role of regulatory T cells that suppress Th1 and Th17 effector cell responses and whose immunosuppressive activity is impaired in patients with multiple sclerosis. Those recent observations suggest that a defect in self-tolerance homeostasis might be the primary mover of multiple sclerosis leading to subsequent immune attacks, inflammation and neurodegeneration. The concept of multiple sclerosis as a consequence of the failure of central and peripheral tolerance mechanisms to maintain a self-tolerance state, particularly of regulatory T cells, may have therapeutic implications. Restoring normal thymic output and suppressive functions of regulatory T cells appears an appealing approach. Regulatory T cells suppress the general local immune response via bystander effects rather than through individual antigen-specific responses. Interestingly, the beneficial effects of currently approved immunomodulators (interferons β and glatiramer acetate) are associated with a restored regulatory T cell homeostasis. However, the feedback regulation between Th1 and Th17 effector cells and regulatory T cells is not so simple and tolerogenic mechanisms also involve other regulatory cells such as B cells, dendritic cells and CD56(bright) natural killer cells." @default.
• W1999712988 created "2016-06-24" @default.
• W1999712988 creator A5031798576 @default.
• W1999712988 date "2012-03-24" @default.
• W1999712988 modified "2023-09-25" @default.
• W1999712988 title "Self-tolerance in multiple sclerosis" @default.
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• W1999712988 doi "https://doi.org/10.1007/s13760-012-0061-x" @default.
• W1999712988 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3375076" @default.
• W1999712988 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22450711" @default.

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