期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms22052560
关键词
interferon stimulated genes; IFNLR1; knockout; transcriptome
资金
- MH CZ-DRO Institute for Clinical and Experimental Medicine-IKEM [IN 00023001]
- Czech Ministry of Education, Youth and Sports [LTC19040]
- DFG [STR1095/6-1]
The study examined the signaling pathways of Lambda interferons in liver-derived cell lines and the association of a specific variant with hepatitis C. Results showed that transfection with non-tagged IFNL3 and IFNL4 did not induce transcriptome changes in cells lacking specific receptor subunits. Additionally, the data did not support the hypothesis of IFNL4-specific non-canonical signaling and urged caution in interpreting functional studies conducted with tagged interferons.
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.
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