Abstract
The TNF superfamily cytokine, lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T cells (LIGHT; TNFSF14), can augment T cell responses inducing IFN-gamma production and can drive pathological gut inflammation when expressed as a transgene in mouse T cells. LIGHT expression by human intestinal T cells suggests the possibility that LIGHT may play a key role in regulation of the mucosal immune system. A nonenzymatic method was developed for the isolation of T cells from the human lamina propria, permitting analysis of native cell surface protein expression. Cell surface LIGHT was constitutively expressed on mucosal T and NK cells and a subpopulation of gut-homing CD4(+) T cells in the periphery. In addition, CD2-mediated stimulation induced efficient LIGHT expression on intestinal CD4(+) T cells, but not on peripheral blood T cells, suggesting a gut-specific, Ag-independent mechanism for LIGHT induction. By contrast, herpesvirus entry mediator expression on gut T cells was unperturbed, implicating the transcriptional regulation of LIGHT as a mechanism modulating signaling activity in the gut. Quantitative analysis of LIGHT mRNA in a cohort of inflammatory bowel disease patients indicated elevated expression in biopsies from small bowel and from inflamed sites, implicating LIGHT as a mediator of mucosal inflammation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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CD2 Antigens / physiology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Humans
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Inflammation / immunology
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Inflammation / metabolism
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Inflammation / pathology
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Inflammatory Bowel Diseases / immunology
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Inflammatory Bowel Diseases / metabolism
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Inflammatory Bowel Diseases / pathology
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / pathology
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Intestine, Small / immunology
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Intestine, Small / metabolism
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Intestine, Small / pathology
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism*
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Lymphocyte Activation
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Membrane Proteins / biosynthesis*
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Membrane Proteins / blood
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Membrane Proteins / genetics*
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RNA, Messenger / biosynthesis
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / immunology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / genetics*
Substances
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CD2 Antigens
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Membrane Proteins
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RNA, Messenger
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus
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TNFRSF14 protein, human
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TNFSF14 protein, human
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Tnfrsf14 protein, mouse
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Tnfsf14 protein, mouse
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha