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

Lookup NU author(s): Professor Catharien HilkensORCiD

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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.

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Journal of Immunology

Year: 2003

Volume: 171

Issue: 10

Pages: 5255-5263

Print publication date: 15/11/2003

ISSN (print): 0022-1767

ISSN (electronic): 1550-6606

Publisher: American Association of Immunologists

URL: http://www.jimmunol.org/cgi/reprint/171/10/5255

Notes: 0022-1767 Journal Article

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