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Genetic deficiency of Irgm1 (LRG‐47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4 + T cells
Author(s) -
Xu Hongwei,
Wu ZhiYing,
Fang Fang,
Guo Lan,
Chen Doris,
Chen John Xi,
Stern David,
Taylor Gregory A.,
Jiang Hong,
Yan Shirley ShiDu
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-137323
Subject(s) - experimental autoimmune encephalomyelitis , multiple sclerosis , biology , microbiology and biotechnology , pathogenesis , apoptosis , immunology , microglia , inflammation , biochemistry
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.—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