Expression of Interferons Lambda 3 and 4 Induces Identical Response in Human Liver Cell Lines Depending Exclusively on Canonical Signaling

0544867 - ÚMG 2022 RIV CH eng J - Článek v odborném periodiku
Lunova, M. - Kubovčiak, Jan - Smolková, Barbora - Uzhytchak, Mariia - Michalová, K. - Dejneka, Alexandr - Strnad, P. - Lunov, Oleg - Jirsa, M.
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. Roč. 22, č. 5 (2021), č. článku 2560. E-ISSN 1422-0067
Grant CEP: GA MŠMT LTC19040
Institucionální podpora: RVO:68378050 ; RVO:68378271
Klíčová slova: interferon stimulated genes * ifnlr1 * knockout * transcriptome
Obor OECD: Biochemistry and molecular biology; Cell biology (FZU-D)
Impakt faktor: 6.208, rok: 2021
Způsob publikování: Open access

Lambda interferons mediate antiviral immunity by inducing interferon-stimulated genes (ISGs) in epithelial tissues. A common variant rs368234815TT/ increment 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.
Trvalý link: http://hdl.handle.net/11104/0321665