4.8 Article

Targeted Expression of Myelin Autoantigen in the Periphery Induces Antigen-Specific T and B Cell Tolerance and Ameliorates Autoimmune Disease

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.668487

Keywords

experimental autoimmue encephalomyelitis; tolerance; autoimmunity; multiple sclerosis (MS); MOG (myelin oligodendrocyte glycoprotein)

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Funding

  1. Max Planck Society
  2. European Research Council starting grant (GAMES) [635617]
  3. German research foundation (DFG) [SFB TR-128]

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The study demonstrates that ectopic expression of MOG in immune organs can induce MOG-specific tolerance and long-lasting protection, potentially serving as a therapeutic strategy for specific autoantigen-driven autoimmune diseases.
There is a great interest in developing antigen-specific therapeutic approaches for the treatment of autoimmune diseases without compromising normal immune function. The key challenges are to control all antigen-specific lymphocyte populations that contribute to pathogenic inflammatory processes and to provide long-term protection from disease relapses. Here, we show that myelin oligodendrocyte glycoprotein (MOG)-specific tolerance can be established by ectopic expression of MOG in the immune organs. Using transgenic mice expressing MOG-specific CD4, CD8, and B cell receptors, we show that MOG expression in the bone marrow cells results in impaired development of MOG-specific lymphocytes. Ectopic MOG expression has also resulted in long-lasting protection from MOG-induced autoimmunity. This finding raises hope that transplantation of autoantigen-expressing bone marrow cells as a therapeutic strategy for specific autoantigen-driven autoimmune diseases.

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