Abstract
Harnessing DCs for immunotherapies in vivo requires the elucidation of the physiological role of distinct DC populations. Migratory DCs traffic from peripheral tissues to draining lymph nodes charged with tissue self antigens. We hypothesized that these DC populations have a specialized role in the maintenance of peripheral tolerance, specifically, to generate suppressive Foxp3+ Tregs. To examine the differential capacity of migratory DCs versus blood-derived lymphoid-resident DCs for Treg generation in vivo, we targeted a self antigen, myelin oligodendrocyte glycoprotein, using antibodies against cell surface receptors differentially expressed in these DC populations. Using this approach together with mouse models that lack specific DC populations, we found that migratory DCs have a superior ability to generate Tregs in vivo, which in turn drastically improve the outcome of experimental autoimmune encephalomyelitis. These results provide a rationale for the development of novel therapies targeting migratory DCs for the treatment of autoimmune diseases.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigens, CD / immunology
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Antigens, Surface / immunology
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Autoantigens
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Cell Movement / immunology
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Dendritic Cells / classification
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Dendritic Cells / immunology*
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Dendritic Cells / physiology
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Forkhead Transcription Factors / metabolism
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Langerhans Cells / immunology
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Langerhans Cells / physiology
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Lectins, C-Type / antagonists & inhibitors
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Lectins, C-Type / deficiency
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Mannose-Binding Lectins / antagonists & inhibitors
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Mannose-Binding Lectins / immunology
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Mice
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Mice, Knockout
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Minor Histocompatibility Antigens
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Myelin-Oligodendrocyte Glycoprotein / immunology
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Peripheral Tolerance / immunology*
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Peripheral Tolerance / physiology
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / immunology
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Receptors, Immunologic / deficiency
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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T-Lymphocytes, Regulatory / immunology
Substances
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Antigens, CD
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Antigens, Surface
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Autoantigens
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Cd207 protein, mouse
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DEC-205 receptor
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Dcir protein, mouse
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Lectins, C-Type
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Mannose-Binding Lectins
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Minor Histocompatibility Antigens
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Mog protein, mouse
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Myelin-Oligodendrocyte Glycoprotein
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Receptors, Cell Surface
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Receptors, Immunologic
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Treml4 protein, mouse