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干扰素 lambda 3 和 4 的表达在人类肝细胞系中诱导相同的反应，完全依赖于经典信号通路。

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

机构信息

Institute for Clinical & Experimental Medicine (IKEM), 14021 Prague, Czech Republic.

Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic.

出版信息

Int J Mol Sci. 2021 Mar 4;22(5):2560. doi: 10.3390/ijms22052560.

DOI:10.3390/ijms22052560
PMID:33806448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7961969/
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.

摘要

λ 干扰素通过诱导上皮组织中的干扰素刺激基因 (ISGs) 来介导抗病毒免疫。一个常见的变异 rs368234815TT/∆G 从 IFNL4 假基因中创造出功能性基因，与肝脏中主要 ISGs 的表达相关，但丙型肝炎的清除能力受损。为了解释这一点，我们比较了肝源性细胞系中标记和未标记的 IFNL3 和 IFNL4 信号转导。转染非标记的 IFNL3、非标记的 IFNL4 和 Halo 标记的 IFNL4 导致相似程度的 JAK-STAT 激活和 ISG 诱导；然而，转染 Halo 标记的 IFNL3 的反应较低且延迟。在缺乏 IL10R2 或 IFNLR1 受体亚单位的细胞中转染非标记的 IFNL3 或 IFNL4 不会引起转录组变化。在野生型细胞中细胞质过表达缺乏信号肽的 IFNL3 或 IFNL4 不会干扰培养基中干扰素触发的 JAK-STAT 信号转导。最后，非标记的 IFNL3 和 IFNL4 转染诱导的表达谱变化高度相似。这些数据不支持关于 IFNL4 特异性非经典信号的假设，并指出应该谨慎解释用标记干扰素进行的功能研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/6ab191de056a/ijms-22-02560-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/bf103710b130/ijms-22-02560-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/6ab191de056a/ijms-22-02560-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/a6780db17ec1/ijms-22-02560-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/a81ab94cb883/ijms-22-02560-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/d4c865554732/ijms-22-02560-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/e6fc8360077b/ijms-22-02560-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/421ae5484b8d/ijms-22-02560-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/bf103710b130/ijms-22-02560-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8572/7961969/6ab191de056a/ijms-22-02560-g007.jpg

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