Endogenously produced TNF-α contributes to the expression of CXCL10/IP-10 in IFN-λ3-activated plasmacytoid dendritic cells.

Abstract

The interplay between IFN-λs and dendritic cells is becoming increasingly relevant, particularly in light of their key role in inducing the antiviral state, including in hepatitis C virus infection. In this work, we have analyzed extensively how human plasmacytoid dendritic cells respond to IFN-λ3. We report that plasmacytoid dendritic cells incubated with IFN-λ3 prolong their survival; alter their expression pattern of surface HLA-DRα, CD123, CD86, and CD303; and time dependently produce IFN-α, CXCL10/IFN-γ-induced protein 10, and even modest quantities of TNF-α. Nevertheless, endogenously produced TNF-α, but not IFN-α, was found to be essential for driving the expression of CXCL10/IFN-γ-induced protein 10 in IFN-λ3-treated plasmacytoid dendritic cells, as revealed by neutralizing experiments by use of adalimumab, etanercept, and infliximab. We also observed that based on the kinetics and levels of IFN-α and CXCL10/IFN-γ-induced protein 10 produced by their IFN-λ3-treated plasmacytoid dendritic cells, healthy donors could be categorized into 2 and 3 groups, respectively. In particular, we identified a group of donors whose plasmacytoid dendritic cells produced modest quantities of CXCL10/IFN-γ-induced protein 10; another one whose plasmacytoid dendritic cells produced elevated CXCL10/IFN-γ-induced protein 10 levels, already after 18 h, declining thereafter; and a 3rd group characterized by plasmacytoid dendritic cells releasing very high CXCL10/IFN-γ-induced protein 10 levels after 42 h only. Finally, we report that in plasmacytoid dendritic cells, equivalent concentrations of IFN-λ3 and IFN-λ1 promote survival, antigen modulation, and cytokine production in a comparable manner and without acting additively/synergistically. Altogether, data not only extend the knowledge on the biologic effects that IFN-λs exert on plasmacytoid dendritic cells but also add novel light to the networking between IFN-λs and plasmacytoid dendritic cells in fighting viral diseases.

• Authors: Giulia Finotti, Nicola Tamassia, Federica Calzetti, Giovanna Fattovich, Marco A Cassatella
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 99 Issue 1 Pg. 107-19 (Jan 2016) ISSN: 1938-3673 [Electronic] England
• PMID: 26382296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Society for Leukocyte Biology.

Chemical References

• Antigens, Surface
• Chemokine CXCL10
• Cytokines
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Antigens, Surface (metabolism)
• Cell Survival (drug effects)
• Cells, Cultured
• Chemokine CXCL10 (metabolism)
• Cytokines (metabolism)
• Dendritic Cells (drug effects, immunology, metabolism)
• Gene Expression
• Humans
• Immunity, Innate
• Interferon-gamma (pharmacology)
• Tumor Necrosis Factor-alpha (biosynthesis)