Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells Journal Article
| Authors: | Xu, H.; Wu, Z. Y.; Fang, F.; Guo, L.; Chen, D.; Chen, J. X.; Stern, D.; Taylor, G. A.; Jiang, H.; Yan, S. S. |
| Article Title: | Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells |
| Abstract: | 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)-γ 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. © FASEB. |
| Keywords: | human tissue; genetics; interferon; nonhuman; myelin basic protein; animal cell; mouse; animal; mouse mutant; animals; mice; mice, knockout; gene; mus; apoptosis; gene expression; spleen; animal experiment; animal model; gtp-binding proteins; central nervous system; animalia; immunology; lymphocyte activation; gamma interferon; spinal cord; cd4+ t lymphocyte; cd4-positive t-lymphocytes; upregulation; interferon-gamma; multiple sclerosis; guanine nucleotide binding protein; allergic encephalomyelitis; eae/ms; ifn-γ-mediated apoptosis; ifi1 protein, mouse; irgm1 gene; mononuclear phagocyte; encephalomyelitis, autoimmune, experimental |
| Journal Title: | FASEB Journal |
| Volume: | 24 |
| Issue: | 5 |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2010-05-01 |
| Start Page: | 1583 |
| End Page: | 1592 |
| Language: | English |
| DOI: | 10.1096/fj.09-137323 |
| PUBMED: | 20056715 |
| PROVIDER: | scopus |
| PMCID: | PMC2879948 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: FAJOE" - "Source: Scopus" |
