Abstract
MiR-155 (-/-) mice are highly resistant to experimental autoimmune encephalomyelitis (EAE), while Pdcd1 (-/-) mice develop a more severe form of the disease. To determine the conflicting roles of these two molecules in the disease, we generated miR-155 (-/-) Pdcd1 (-/-) double knockout (DKO) mice. We found that ablation of programmed cell death protein 1 (PD-1) expression in miR-155-deficient mice restored the susceptibility to EAE. The increased severity of the disease in DKO mice was accompanied by an enhanced T-cell infiltration into the brain as well as an increased production of pro-inflammatory cytokines IFN-γ and IL-17. Furthermore, the major contribution of the DKO to EAE was T-cell intrinsic since adoptive transfer of CD4(+) T cells from DKO donors promoted the disease in lymphopenic recipients. These results define PD-1 deficiency in miR-155 (-/-) mice as a promoting factor of autoimmune inflammation by increasing antigen-driven T-cell expansion and infiltration.
Keywords:
IFN-γ; IL-17; autoimmunity; inflammation; microRNA.
© The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Brain / immunology
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Brain / pathology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / pathology
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CD4-Positive T-Lymphocytes / transplantation
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Cell Movement
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Disease Susceptibility
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / genetics*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Gene Expression Regulation
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Interferon-gamma / biosynthesis
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Interferon-gamma / metabolism
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Interleukin-17 / biosynthesis
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Interleukin-17 / metabolism
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Mice
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Mice, Knockout
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MicroRNAs / genetics
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MicroRNAs / immunology*
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Mycobacterium tuberculosis / immunology
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Mycobacterium tuberculosis / pathogenicity
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Programmed Cell Death 1 Receptor / deficiency
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Programmed Cell Death 1 Receptor / genetics
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Programmed Cell Death 1 Receptor / immunology*
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Severity of Illness Index
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Signal Transduction
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Spleen / immunology
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Spleen / pathology
Substances
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Interleukin-17
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MicroRNAs
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Mirn155 microRNA, mouse
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Myelin-Oligodendrocyte Glycoprotein
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Pdcd1 protein, mouse
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Peptide Fragments
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Programmed Cell Death 1 Receptor
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myelin oligodendrocyte glycoprotein (35-55)
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Interferon-gamma