Differential activity of type I interferon subtypes for dendritic cell differentiation

PLoS One. 2013;8(3):e58465. doi: 10.1371/journal.pone.0058465. Epub 2013 Mar 5.

Abstract

The type I interferon (IFN) family comprises 15 cytokines (in human 13α, 1β, 1ω), which exert several cellular functions through binding to a common receptor. Despite initial activation of the same Jak/Stat signalling pathway, the cellular response may differ depending on type I IFN subtype. We investigated the activity of six type I IFN subtypes - IFNα1, α2, α8, α21, ω and β- to promote the differentiation of dendritic cells (DC). Transcriptome analyses identified two distinct groups, the IFNα/ω-DC and the IFNβ-DC. In addition, the expression level of seven chemokines and several cell surface markers characteristic of DC distinguished IFNα-DC and IFNβ-DC. These differences are unlikely to impact the efficacy of T cell functional response since IFNα2-DC and IFNβ-DC were equipotent in inducing the proliferation and the polarization of allogenic naïve CD4 T cells into Th1 cells and in stimulating autologous antigen specific CD4 or CD8 T cells. Of the functional parameters analysed, the only one that showed a modest differential was the phagocytic uptake of dead cells which was higher for IFNα2-DC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Differentiation
  • Cell Membrane / metabolism
  • Cell Proliferation
  • Chemotaxis
  • Cytokines / metabolism
  • Dendritic Cells / cytology*
  • Gene Expression Profiling
  • Humans
  • Interferon Type I / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Phagocytosis
  • RNA / metabolism
  • Signal Transduction
  • Th1 Cells / cytology
  • Transcriptome

Substances

  • Cytokines
  • Interferon Type I
  • RNA

Grants and funding

Funding was from the European Community's Seventh Framework Programme under grant agreement n° 223608 (GU and JP). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.