Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01

AUTHORS

E M Giles, T J Sanders, N E McCarthy, J Lung, M Pathak, T T MacDonald, J O Lindsay, A J Stagg

ABSTRACT

Type 1 interferon (IFN-1) promotes regulatory T-cell function to suppress inflammation in the mouse intestine, but little is known about IFN-1 in the human gut. We therefore assessed the influence of IFN-1 on CD4+ T-cells isolated from human colon tissue obtained from healthy controls or patients with inflammatory bowel disease (IBD). Immunofluorescent imaging revealed constitutive expression of IFNβ in human intestinal tissue, and colonic T-cells were responsive to exogenous IFN-1 as assessed by phosphorylation of signal transduction and activator of transcription 1 (pSTAT1) and induction of interferon stimulated genes (ISGs). Unlike their blood counterparts, intestinal T-cells from non-inflamed regions of IBD colon displayed enhanced responsiveness to IFN-1, increased frequency of pSTAT1+ cells, and greater induction of ISGs upon IFN-1 exposure in vitro. In healthy tissue, antibody neutralization of IFNβ selectively reduced T-cell production of the pro-regulatory cytokine interleukin-10 (IL-10) and increased IFNγ synthesis. In contrast, neutralization of IFNβ in IBD tissue cultures increased the frequency of T-cells producing inflammatory cytokines but did not alter IL-10 expression. These data support a role for endogenous IFN-1 as a context-dependent modulator of T-cell function that promotes regulatory activity in healthy human intestine, but indicate that the IFN-1/STAT1 pathway is dysregulated in inflammatory bowel disease. More... »

PAGES

184

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/mi.2016.44

DOI

http://dx.doi.org/10.1038/mi.2016.44

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022290483

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27220814


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RDF/XML is a standard XML format for linked data.

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