Expression of Interferons Lambda 3 and 4 Induces Identical Response in Human Liver Cell Lines Depending Exclusively on Canonical Signaling
International Journal of Molecular Sciences, vol. 22, pp. 2560
Abstract
Lambda interferons mediate antiviral immunity by inducing interferon-stimulated genes (ISGs) in epithelial tissues. A common variant rs368234815TT/∆G creating functional gene from an IFNL4 pseudogene is associated with the expression of major ISGs in the liver but impaired clearance of hepatitis C. To explain this, we compared Halo-tagged and non-tagged IFNL3 and IFNL4 signaling in liver-derived cell lines. Transfection with non-tagged IFNL3, non-tagged IFNL4 and Halo-tagged IFNL4 led to a similar degree of JAK-STAT activation and ISG induction; however, the response to transfection with Halo-tagged IFNL3 was lower and delayed. Transfection with non-tagged IFNL3 or IFNL4 induced no transcriptome change in the cells lacking either IL10R2 or IFNLR1 receptor subunits. Cytosolic overexpression of signal peptide-lacking IFNL3 or IFNL4 in wild type cells did not interfere with JAK-STAT signaling triggered by interferons in the medium. Finally, expression profile changes induced by transfection with non-tagged IFNL3 and IFNL4 were highly similar. These data do not support the hypothesis about IFNL4-specific non-canonical signaling and point out that functional studies conducted with tagged interferons should be interpreted with caution.
Authors 9
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Mariia Lunová corresponding
Institute of Clinical and Experimental Medicine
Affiliation as printed
Institute for Clinical & Experimental Medicine (IKEM), 14021 Prague, Czech Republic
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Czech Academy of Sciences, Institute of Molecular Genetics
Affiliation as printed
Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic
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Czech Academy of Sciences · FZU - Institute of Physics of the Czech Academy of Sciences
Affiliation as printed
Department of Optical and Biophysical Systems, Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
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Czech Academy of Sciences · FZU - Institute of Physics of the Czech Academy of Sciences
Affiliation as printed
Department of Optical and Biophysical Systems, Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
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Charles University · General University Hospital in Prague
Affiliation as printed
Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine of Charles University, 12808 Prague, Czech Republic
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Czech Academy of Sciences · FZU - Institute of Physics of the Czech Academy of Sciences
Affiliation as printed
Department of Optical and Biophysical Systems, Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Internal Medicine III, University Hospital RWTH (Rheinisch-Westfälisch Technische Hochschule) Aachen, 52062 Aachen, Germany
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Czech Academy of Sciences · FZU - Institute of Physics of the Czech Academy of Sciences
Affiliation as printed
Department of Optical and Biophysical Systems, Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
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Charles University · Institute of Clinical and Experimental Medicine · General University Hospital in Prague
Affiliation as printed
Institute for Clinical & Experimental Medicine (IKEM), 14021 Prague, Czech Republic
Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine of Charles University, 12808 Prague, Czech Republic
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