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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-14187

Lüth, S; Huber, S; Schramm, C; Buch, T; Zander, S; Stadelmann, C; Brück, W; Wraith, D C; Herkel, J; Lohse, A W (2008). Ectopic expression of neural autoantigen in mouse liver suppresses experimental autoimmune neuroinflammation by inducing antigen-specific Tregs. Journal of Clinical Investigation, 118(10):3403-10.

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Abstract

Tregs are important mediators of immune tolerance to self antigens, and it has been suggested that Treg inactivation may cause autoimmune disease. Therefore, immunotherapy approaches that aim to restore or expand autoantigen-specific Treg activity might be beneficial for the treatment of autoimmune disease. Here we report that Treg-mediated suppression of autoimmune disease can be achieved in vivo by taking advantage of the ability of the liver to promote immune tolerance. Expression of the neural autoantigen myelin basic protein (MBP) in the liver was accomplished stably in liver-specific MBP transgenic mice and transiently using gene transfer to liver cells in vivo. Such ectopic MBP expression induced protection from autoimmune neuroinflammation in a mouse model of multiple sclerosis. Protection from autoimmunity was mediated by MBP-specific CD4+CD25+Foxp3+ Tregs, as demonstrated by the ability of these cells to prevent disease when adoptively transferred into nontransgenic mice and to suppress conventional CD4+CD25- T cell proliferation after antigen-specific stimulation with MBP in vitro. The generation of MBP-specific CD4+CD25+Foxp3+ Tregs in vivo depended on expression of MBP in the liver, but not in skin, and occurred by TGF-beta-dependent peripheral conversion from conventional non-Tregs. Our findings indicate that autoantigen expression in the liver may generate autoantigen-specific Tregs. Thus, targeting of autoantigens to hepatocytes may be a novel approach to prevention or treatment of autoimmune diseases.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
DDC:570 Life sciences; biology
610 Medicine & health
Date:2008
Deposited On:10 Feb 2011 15:17
Last Modified:14 Dec 2013 22:41
Publisher:American Society for Clinical Investigation
ISSN:0021-9738
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1172/JCI32132
PubMed ID:18802476
Citations:Web of Science®. Times Cited: 60
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Scopus®. Citation Count: 62

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