Abstract
T-regulatory cells expressing the forkhead box transcription factor 3 (Foxp3) play essential roles in immune homeostasis. Experimental autoimmune neuritis (EAN) is an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system. We investigated the distribution of Foxp3(+) cells in sciatic nerves, spleen and lymph nodes of EAN rats, and the influence of FTY720 on the localization of Foxp3(+) cells in EAN rats. In sciatic nerves of EAN rats, accumulation of Foxp3(+) cells was not seen during the pre-symptomatic phase (until Day 9) or during early or peak disease activity. In contrast, Foxp3(+) cell accumulation was regularly seen in the recovery from neurologic disease, suggesting a contribution of Foxp3(+) cells to the resolution of EAN. FTY720 was given at onset of EAN (Day 10) until Day 18. Following FTY720 administration, percentages of Foxp3(+) cells in EAN rats were increased in circulating blood, but reduced in lymph nodes compared to the PBS control. FTY720 treatment suppressed total numbers but increased percentages of Foxp3(+) cells in sciatic nerves of EAN rats. These data not only suggests a protective role of Foxp3(+) cells in EAN but also provides a potential way to alter localization of Foxp3(+) cells in vivo.
MeSH terms
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Animals
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Cell Proliferation / drug effects
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Disease Models, Animal
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Down-Regulation / drug effects
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Down-Regulation / immunology
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Fingolimod Hydrochloride
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Forkhead Transcription Factors / analysis
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Forkhead Transcription Factors / metabolism*
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Immunity, Cellular / drug effects
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Immunity, Cellular / immunology
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Immunosuppressive Agents / pharmacology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymph Nodes / physiopathology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Lymphocyte Count
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Lymphoid Tissue / immunology*
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Lymphoid Tissue / metabolism
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Lymphoid Tissue / physiopathology
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Male
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Neuritis, Autoimmune, Experimental / immunology
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Neuritis, Autoimmune, Experimental / metabolism
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Neuritis, Autoimmune, Experimental / physiopathology
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Polyradiculoneuropathy / immunology*
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Polyradiculoneuropathy / metabolism
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Polyradiculoneuropathy / physiopathology
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Propylene Glycols / pharmacology
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Rats
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Rats, Inbred Lew
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Sciatic Nerve / immunology*
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Sciatic Nerve / metabolism
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Sciatic Nerve / physiopathology
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Sphingosine / analogs & derivatives
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Sphingosine / pharmacology
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Spleen / immunology
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Spleen / metabolism
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Spleen / physiopathology
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
Substances
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Forkhead Transcription Factors
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Foxp3 protein, rat
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Immunosuppressive Agents
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Propylene Glycols
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Fingolimod Hydrochloride
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Sphingosine