Publication:

Differential Responses to IFN-α Subtypes in Human T Cells and Dendritic Cells (2003)

Author(s): Hilkens CM, Schlaak JF, Kerr IM

  • : Differential responses to IFN-alpha subtypes in human T cells and dendritic cells

Abstract: Type I IFNs (IFN-alphabeta) constitute a family of cytokines that have important antiviral and immunoregulatory properties and have been successfully used in the treatment of a wide variety of diseases. There are 12 functional human IFN-alpha subtypes and one IFN-beta subtype that signal through the common cell surface IFN-alphabetaR. To date, virtually no information is available on the specificity of IFN-alpha responses in immune cells. In this study, Janus kinase/STAT signaling and transcriptional responses to selected IFN-alpha subtypes in human T cells and dendritic cells were analyzed. Evidence for IFN-alpha subtype and cell type specificity was found. Also, differences between kinetics of expression of IFN-stimulated genes (ISGs) and in the requirements of individual ISGs for additional signaling pathways were observed. In particular, IFN-gamma-inducible protein-10 (IP-10), a key chemokine in Th1-type inflammatory diseases, was differentially regulated. In dendritic cells, it was highly induced by IFN-alpha2 and IFN-alpha21 but much less efficiently by IFN-alpha1. It was only marginally induced by these subtypes in T cells. In marked contrast to other ISGs analyzed, optimum induction of IP-10 was dependent on activation of p38 kinase(s). The observed variations (subtype-, cell type-, and ISG-related differentials) provide further insight into the complexity and plasticity of the IFN-alphabeta response. Furthermore, the novel observation that IFN-alpha1 poorly induces IP-10 is potentially of clinical importance, because this subtype may be more beneficial in cases where Th1-mediated side effects (e.g., exacerbation of autoimmune diseases) are not desirable.

Notes: 0022-1767 Journal Article

  • Short Title: Differential responses to IFN-alpha subtypes in human T cells and dendritic cells
  • Date: 2003-11-15
  • Journal: Journal of Immunology
  • Volume: 171
  • Issue: 10
  • Pages: 5255-5263
  • Publisher: American Association of Immunologists
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Cells, Cultured Chemokines, CXC/biosynthesis/genetics Comparative Study DNA-Binding Proteins/biosynthesis/genetics/metabolism Dendritic Cells/enzymology/*immunology/metabolism Enzyme Activation/immunology Gene Expression Profiling Human Interferon-alpha/*classification/*pharmacology Kinetics MAP Kinase Signaling System/genetics/immunology Mitogen-Activated Protein Kinases/metabolism/physiology Nitric-Oxide Synthase/biosynthesis/genetics RNA, Messenger/biosynthesis Receptors, Interleukin/biosynthesis/genetics Support, Non-U.S. Gov't T-Lymphocytes/enzymology/*immunology/metabolism Trans-Activators/biosynthesis/genetics/metabolism

Staff

Dr Catharien Hilkens
Reader in Immunotherapy