Abstract
The cytokine interleukin IL-35 is known to exert strong immunosuppressive functions. Indoleamine 2,3-dioxygenase 1 (IDO1) and Arginase 1 (Arg1) are metabolic enzymes that, expressed by dendritic cells (DCs), contribute to immunoregulation. Here, we explored any possible link between IL-35 and the activity of those enzymes. We transfected a single chain IL-35Ig gene construct in murine splenic DCs (DC35 ) and assessed any IDO1 and Arg1 activities as resulting from ectopic IL-35Ig expression, both in vitro and in vivo. Unlike Ido1, Arg1 expression was induced in vitro in DC35 , and it conferred an immunosuppressive phenotype on those cells, as revealed by a delayed-type hypersensitivity assay. Moreover, the in vivo onset of a tolerogenic phenotype in DC35 was associated with the detection of CD25+ CD39+ , rather than Foxp3+ , regulatory T cells. Therefore, Arg1, but not Ido1, expression in DC35 appears to be an early event in IL-35Ig-mediated immunosuppression.
Keywords:
IDO1; IL-35; arginase 1; dendritic cells; tolerance.
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Apyrase / immunology
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Apyrase / metabolism
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Arginase / genetics
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Arginase / immunology*
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Arginase / metabolism
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Female
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Forkhead Transcription Factors / immunology
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Forkhead Transcription Factors / metabolism
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Immune Tolerance / genetics
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Immune Tolerance / immunology*
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Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
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Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
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Interleukin-2 Receptor alpha Subunit / immunology
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Interleukin-2 Receptor alpha Subunit / metabolism
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Interleukin-4 / genetics
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Interleukins / genetics
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Interleukins / immunology*
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Interleukins / metabolism
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Mice, Inbred C57BL
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Mice, Knockout
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / immunology
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Transforming Growth Factor beta / metabolism
Substances
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Antigens, CD
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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IDO1 protein, mouse
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Interleukin-2 Receptor alpha Subunit
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Interleukins
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Transforming Growth Factor beta
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interleukin-35, mouse
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Interleukin-4
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Arg1 protein, mouse
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Arginase
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Apyrase
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CD39 antigen