Journal
FASEB JOURNAL
Volume 24, Issue 5, Pages 1583-1592Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.09-137323
Keywords
IFN-gamma-mediated apoptosis; EAE/MS; animal model
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Funding
- National Institute of Neurological Disorders and Stroke grant [NINDS 042855]
- U. S. National Institutes of Health [AI-57831]
- Veterans Affairs Merit Review
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The immunity-related GTPase Irgm1, also called LRG-47, is known to regulate host resistance to intracellular pathogens through multiple mechanisms that include controlling the survival of T lymphocytes. Here, we address whether Irgm1 also plays a role in the pathogenesis of experimental autoimmune encephalitis (EAE). We find that Irgm1/LRG-47 is a significant factor in the progression of EAE and multiple sclerosis (MS). Expression of Irgm1 was robustly elevated in MS-affected lesions and in the central nervous system (CNS) of myelin basic protein (MBP)-induced EAE mice, especially in cells of lymphoid and mononuclear phagocyte origin. Homozygous Irgm1 null mice were resistant to MBP-induced EAE, and CD4(+) T cells in spleen and CNS of these mice displayed decreased proliferative capacity, increased apoptosis, and up-regulated interferon (IFN)-gamma induction. Therefore, Irgm1-induced survival of autoreactive CD4(+) T cells contributes significantly to the pathogenesis of EAE. Blockade of Irgm1 may be a potential therapeutic strategy for halting multiple sclerosis.-Xu, H., Wu, Z.-Y., Fang, F., Guo, L., Chen, D., Chen, J. X., Stern, D., Taylor, G. A., Jiang, H., Yan, S. S. Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4(+) T cells. FASEB J. 24, 1583-1592 (2010). www.fasebj.org
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