Abstract
Reactive oxygen species are used by the immune system to eliminate infections; however, they may also serve as signaling intermediates to coordinate the efforts of the innate and adaptive immune systems. In this study, we show that by eliminating macrophage and T cell superoxide production through the NADPH oxidase (NOX), T cell polarization was altered. After stimulation with immobilized anti-CD3 and anti-CD28 or priming recall, T cells from NOX-deficient mice exhibited a skewed Th17 phenotype, whereas NOX-intact cells produced cytokines indicative of a Th1 response. These findings were corroborated in vivo by studying two different autoimmune diseases mediated by Th17 or Th1 pathogenic T cell responses. NOX-deficient NOD mice were Th17 prone with a concomitant susceptibility to experimental allergic encephalomyelitis and significant protection against type 1 diabetes. These data validate the role of superoxide in shaping Th responses and as a signaling intermediate to modulate Th17 and Th1 T cell responses.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmunity / immunology*
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Blotting, Western
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Cell Lineage / immunology*
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Cell Separation
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Cytokines / biosynthesis
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Cytokines / immunology
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Enzyme-Linked Immunosorbent Assay
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Female
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Flow Cytometry
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Interleukin-17 / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred NOD
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Mice, Transgenic
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NADPH Oxidases / deficiency*
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NADPH Oxidases / immunology
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Reactive Oxygen Species / immunology
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Reactive Oxygen Species / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Superoxides / immunology*
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / enzymology
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes, Helper-Inducer / cytology*
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T-Lymphocytes, Helper-Inducer / enzymology
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T-Lymphocytes, Helper-Inducer / immunology
Substances
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Cytokines
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Interleukin-17
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Reactive Oxygen Species
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Superoxides
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NADPH Oxidases