Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Xu, H; Wu, Z-Y; Fang, F; Guo, L; Chen, D; Chen, JX; Stern, D; Taylor, GA; Jiang, H; Yan, SS

Published Date

  • May 2010

Published In

Volume / Issue

  • 24 / 5

Start / End Page

  • 1583 - 1592

PubMed ID

  • 20056715

Pubmed Central ID

  • 20056715

Electronic International Standard Serial Number (EISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.09-137323


  • eng

Conference Location

  • United States