Abstract
Estrogen results in the suppression of experimental allergic encephalomyelitis (EAE), a frequently used experimental animal model of multiple sclerosis (MS). The mechanism by which estrogen acts in diseases with an autoimmune background is less clear. Here, we used splenic dendritic cells (DC) from the Lewis rats EAE model as target cells, and explored the pathway of estrogen in immune modulation. Estrogen did not affect the expression of MHC class II, CD80 and CD86 by DC, but inhibited the ability of DC to stimulate T cell proliferation and production of both Th1 and Th2 cytokines. This was accompanied by increased T cell apoptosis. Estrogen up-regulated DC to express indoleamine 2,3-dioxygenase (IDO) which can limit T cell responses. The effects of estrogen-exposed DC on T cell proliferation and apoptosis were partly abolished by addition of an IDO inhibitor (1-methyl-dl-tryptophan, 1-MT), indicating that estrogen-exposed DC induced IDO-dependent T cell suppression. Our data support the hypothesis that the estrogen-induced suppression of EAE, as well as the reduction in number of MS relapses observed during pregnancy, may be related to the estrogen-DC-IDO axis. This observation could open up a novel therapeutic target for influencing the course of MS and other diseases with an autoimmune diseases background.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / drug effects
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Antigen Presentation / immunology
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Apoptosis / drug effects
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Apoptosis / immunology
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Cell Proliferation / drug effects
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Dendritic Cells / drug effects
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Dendritic Cells / enzymology
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Dendritic Cells / immunology*
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Enzyme Inhibitors / pharmacology
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Estrogens / pharmacology*
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Female
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Gene Expression / genetics
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Lymph Nodes / cytology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Myelin Basic Protein / immunology
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Peptide Fragments / immunology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred Lew
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Tryptophan / analogs & derivatives*
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Tryptophan / pharmacology
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Tryptophan Oxygenase / antagonists & inhibitors
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Tryptophan Oxygenase / genetics
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Tryptophan Oxygenase / metabolism*
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Vaccination
Substances
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Enzyme Inhibitors
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Estrogens
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Myelin Basic Protein
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Peptide Fragments
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RNA, Messenger
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myelin basic protein 68-86
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Interleukin-10
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Interferon-gamma
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Tryptophan
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Tryptophan Oxygenase