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Mol Med. 2015 Jan 6;21:233-41. doi: 10.2119/molmed.2014.00264.

Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion.

Author information

1
Department of Medicine (Cardiovascular Division), Albert Einstein College of Medicine, Bronx, New York, United States of America.
2
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
3
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.
4
Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute of Medical Research, Manhasset, New York, United States of America.
5
Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York, United States of America.

Abstract

Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), is mediated by myelin-specific autoreactive T cells that cause inflammation and demyelination in the central nervous system (CNS), with significant contributions from activated microglia and macrophages. The molecular bases for expansion and activation of these cells, plus trafficking to the CNS for peripheral cells, are not fully understood. Allograft inflammatory factor-1 (Aif-1) (also known as ionized Ca(2+) binding adapter-1 [Iba-1]) is induced in leukocytes in MS and EAE; here we provide the first assessment of Aif-1 function in this setting. After myelin oligodendrocyte glycoprotein peptide (MOG35-55) immunization, Aif-1-deficient mice were less likely than controls to develop EAE and had less CNS leukocyte infiltration and demyelination; their spinal cords contained fewer CD4 T cells and microglia and more CD8 T cells. These mice also showed significantly less splenic CD4 T-cell expansion and activation, plus decreased proinflammatory cytokine expression. These findings identify Aif-1 as a potent molecule that promotes expansion and activation of CD4 T cells, plus elaboration of a proinflammatory cytokine milieu, in MOG35-55-induced EAE and as a potential therapeutic target in MS.

PMID:
25569805
PMCID:
PMC4503655
DOI:
10.2119/molmed.2014.00264
[Indexed for MEDLINE]
Free PMC Article

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