Abstract
Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (Treg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.
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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Adipose Tissue / cytology
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Adipose Tissue / immunology*
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Animals
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / immunology
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Cell Growth Processes / immunology
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Female
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Flow Cytometry
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Gene Expression Regulation
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Homeostasis / immunology
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Interleukin-2 / genetics
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Interleukin-2 / immunology
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Kruppel-Like Transcription Factors / biosynthesis*
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Kruppel-Like Transcription Factors / deficiency
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / immunology
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Macrophages / cytology
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Macrophages / immunology*
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Male
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Mice, Inbred C57BL
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Mice, Knockout
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Natural Killer T-Cells / cytology
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Natural Killer T-Cells / immunology
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Natural Killer T-Cells / metabolism*
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Promyelocytic Leukemia Zinc Finger Protein
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Specific Pathogen-Free Organisms
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism*
Substances
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Basic-Leucine Zipper Transcription Factors
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Interleukin-2
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Kruppel-Like Transcription Factors
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Nfil3 protein, mouse
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Promyelocytic Leukemia Zinc Finger Protein
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Zbtb16 protein, mouse
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Interleukin-10