Abstract
microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little is known about the functional relevance of individual miRNA loci. We identified the miR-17-92 cluster as CD28 costimulation dependent, suggesting that it may be key for Treg development and function. Although overall immune homeostasis was maintained in mice with miR-17-92-deficient Tregs, expression of the miR-17-92 miRNA cluster was critical for Treg accumulation and function during an acute organ-specific autoimmune disease in vivo. Treg-specific loss of miR-17-92 expression resulted in exacerbated experimental autoimmune encephalitis and failure to establish clinical remission. Using peptide-MHC tetramers, we demonstrate that the miR-17-92 cluster was specifically required for the accumulation of activated Ag-specific Treg and for differentiation into IL-10-producing effector Treg.
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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Adult
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Animals
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Antigen Presentation
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Apoptosis Regulatory Proteins / genetics
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Bcl-2-Like Protein 11
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CD28 Antigens / immunology
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Cells, Cultured
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Costimulatory and Inhibitory T-Cell Receptors / immunology
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Epitopes, T-Lymphocyte / immunology
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Gene Deletion
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Heterozygote
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Histocompatibility Antigens Class II / immunology
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Homeostasis
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Humans
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Interleukin-10 / biosynthesis
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Lymphocyte Activation
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Male
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Membrane Proteins / genetics
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Mice
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Mice, Knockout
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MicroRNAs / genetics
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MicroRNAs / immunology*
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Myelin-Oligodendrocyte Glycoprotein / immunology
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PTEN Phosphohydrolase / deficiency
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Peptide Fragments / immunology
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Proto-Oncogene Proteins / genetics
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RNA, Long Noncoding
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Regulatory / immunology*
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Young Adult
Substances
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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CD28 Antigens
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Costimulatory and Inhibitory T-Cell Receptors
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class II
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I-A(b) antigen, mouse
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IL10 protein, mouse
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MIR17HG, human
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MIRN17-92 microRNA, mouse
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Membrane Proteins
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MicroRNAs
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Proto-Oncogene Proteins
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RNA, Long Noncoding
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myelin oligodendrocyte glycoprotein (35-55)
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Interleukin-10
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PTEN Phosphohydrolase
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Pten protein, mouse