Coaxing the liver into preventing autoimmune disease in the brain
Brad E. Hoffman, Roland W. Herzog
Brad E. Hoffman, Roland W. Herzog
Published September 18, 2008
Citation Information: J Clin Invest. 2008;118(10):3271-3273. https://doi.org/10.1172/JCI37079.
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Commentary

Coaxing the liver into preventing autoimmune disease in the brain

Abstract

The liver has several unique immunological properties that affect T cell activation and immune regulation. Recent studies have uncovered opportunities for the treatment of genetic disease by directing expression of the functional therapeutic protein to hepatocytes. In a new study in this issue of the JCI, Lüth and colleagues demonstrate that hepatic expression of a brain protein is protective against neuroinflammatory disease in a mouse model of human MS (see the related article beginning on page 3403). Suppression of autoimmunity was dependent on transgene expression in the liver and was mediated by induction of antigen-specific CD4+CD25+Foxp3+ Tregs. These findings suggest that the introduction of antigens to the liver may have potential as a preventative or therapeutic intervention for autoimmune disease.

Authors

Brad E. Hoffman, Roland W. Herzog

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Figure 1

Prevention of EAE in mice by hepatic expression of MBP.

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Prevention of EAE in mice by hepatic expression of MBP. (A) Immunization...
(A) Immunization with MBP-specific peptide normally causes an inflammatory T cell response in the brain in the EAE mouse model of human MS. (B) In the study by Lüth et al. in this issue of the JCI (20), the authors show that hepatic expression of MBP (normally expressed in the central nervous system), accomplished constitutively in liver-specific MBP transgenic mice (not shown) or transiently after gene transfer to liver cells in vivo, results in induction of MBP-specific CD4+CD25+Foxp3+ Tregs. These MBP-specific CD4+CD25+Foxp3+ Tregs suppressed effector CD4+CD25– T cells and converted conventional CD4+CD25– T cells into CD4+CD25+Foxp3+ Tregs, thereby preventing neuroinflammatory disease. Introduction of antigens to the liver may have potential as a preventative or therapeutic intervention for autoimmune disease.