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

Mucosal Immunol. 2017 Jan;10(1):184-193. doi: 10.1038/mi.2016.44. Epub 2016 May 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antibodies, Blocking / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Child
  • Colon / immunology*
  • Female
  • Humans
  • Immunomodulation
  • Inflammatory Bowel Diseases / immunology*
  • Interferon-beta / immunology
  • Interferon-beta / metabolism*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Lymphocyte Activation
  • Male
  • Mice
  • Phosphorylation
  • STAT1 Transcription Factor / metabolism*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology*


  • Antibodies, Blocking
  • STAT1 Transcription Factor
  • Interleukin-10
  • Interferon-beta
  • Interferon-gamma