Abstract
Although invariant NKT (iNKT) cells participate in many aspects of immune responses, the molecular mechanisms regulating their development, maturation, and activation are still poorly understood. GATA-3 is a T cell-specific transcription factor that is also expressed in iNKT cells. The critical role of GATA-3 in conventional alphabeta T cells has been well documented, but whether GATA-3 also regulates the development and function of iNKT cells is unknown. In the present study, we report that deficiency of GATA-3 results in cell-intrinsic defects in the thymic development and peripheral maturation of murine iNKT cells. In addition, GATA-3 is also required for survival, activation, and effector functions of this unique population of T cells. Our data also reveal a previously unidentified peripheral maturation step that is GATA-3 dependent.
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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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cell Survival / genetics
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Cell Survival / immunology
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Cytokines / biosynthesis
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Cytokines / blood
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GATA3 Transcription Factor / biosynthesis
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GATA3 Transcription Factor / deficiency
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GATA3 Transcription Factor / genetics
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GATA3 Transcription Factor / physiology*
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Galactosylceramides / administration & dosage
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Injections, Intravenous
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Interferon-gamma / biosynthesis
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Killer Cells, Natural / cytology*
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell / physiology
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Signal Transduction / immunology
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Thymus Gland / cytology
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Thymus Gland / immunology
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Thymus Gland / metabolism
Substances
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Cytokines
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GATA3 Transcription Factor
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Galactosylceramides
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Gata3 protein, mouse
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Receptors, Antigen, T-Cell
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alpha-galactosylceramide
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Interferon-gamma