Abstract
IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4(+) T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4(+) T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4(+) T cell activation and that IL-7R antagonism may be effective in treating CD4(+) T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.
Keywords:
EAE; IL-7; Signaling pathways; T cells.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Proliferation
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Cytokines / immunology
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Cytokines / metabolism
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / metabolism
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Flow Cytometry
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Humans
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Interleukin-7 / deficiency
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Interleukin-7 / genetics
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Interleukin-7 / immunology*
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Lymphocyte Activation / immunology*
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Mice, Transgenic
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Phosphorylation / immunology
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Proto-Oncogene Proteins c-akt / immunology
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Proto-Oncogene Proteins c-akt / metabolism
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Interleukin-7 / immunology
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Receptors, Interleukin-7 / metabolism
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STAT2 Transcription Factor / immunology
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STAT2 Transcription Factor / metabolism
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Signal Transduction / immunology
Substances
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Cytokines
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Interleukin-7
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-7
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STAT2 Transcription Factor
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interleukin-7 receptor, alpha chain
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Proto-Oncogene Proteins c-akt