白细胞介素-22 促进细胞增殖以对抗人类肠上皮细胞的病毒感染

IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Interferon and Cytokine Research Pub Date : 2024-10-01 Epub Date: 2024-07-30 DOI:10.1089/jir.2024.0096
Cuncai Guo, Ashwini Kumar Sharma, José Guzmán, Carl Herrmann, Steeve Boulant, Megan L Stanifer
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引用次数: 0

摘要

干扰素λ(IFN-λ)对控制粘膜表面的病毒感染至关重要。有报道称,白细胞介素-22(IL-22)通过帮助诱导干扰素刺激基因(ISGs)或增加细胞增殖从而清除受病毒感染的细胞,帮助 IFN-λ 控制小鼠肠上皮的轮状病毒感染。我们研究了 IL-22 和 IFN-λs 在人类肠上皮细胞(IECs)模型中是否表现出类似的协同作用。我们的结果表明,IL-22 和 IFN-λ 的联合处理比单独使用其中一种细胞因子诱导更多的 STAT1 磷酸化。然而,STAT1激活的增加并没有转化为ISGs生成的增加或抗病毒保护的增加。转录组学分析表明,尽管IL-22和IFN-λ在它们的异源二聚体受体中有一个共同的亚基(IL-10Rb),并激活相似的STATs,但IL-22和IFN-λ产生的信号是独立的,IFN-λ信号诱导ISGs,而IL-22信号诱导细胞增殖基因。我们利用人体肠道器官组织证实,IL-22通过增加细胞增殖和干细胞标志物(OLFM4)的表达来增大器官组织的体积。这些发现表明,在人类肠道细胞中,IFN-λs 和 IL-22 可独立清除病毒感染。IFN-λs 诱导 ISGs 以控制病毒复制和扩散,而 IL-22 增加细胞增殖以清除感染细胞并修复受损上皮细胞。虽然这两种细胞因子不能协同作用,但它们在保护人类 IECs 方面都发挥着关键作用。
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Interleukin-22 Promotes Cell Proliferation to Combat Virus Infection in Human Intestinal Epithelial Cells.

Interferon lambdas (IFN-λs) are crucial to control virus infections at mucosal surfaces. Interleukin-22 (IL-22) was reported to help IFN-λ control rotavirus infection in the intestinal epithelium of mice either by aiding in the induction of interferon-stimulated genes (ISGs) or by increasing cell proliferation thereby clearing virally infected cells. We investigated whether IL-22 and IFN-λs exhibit similar synergistic effects in human intestinal epithelial cells (IECs) models. Our results showed that co-treatment of IL-22 and IFN-λ induced more phosphorylation of STAT1 than either cytokine used alone. However, this increased STAT1 activation did not translate to increased ISGs production or antiviral protection. Transcriptomics analysis revealed that despite sharing a common subunit (IL-10Rb) within their heterodimeric receptors and activating similar STATs, the signaling generated by IL-22 and IFN-λs is independent, with IFN-λ signaling inducing ISGs and IL-22 signaling inducing cell proliferation genes. Using human intestinal organoids, we confirmed that IL-22 increased the size of the organoids through increased cell proliferation and expression of the stem cell marker (OLFM4). These findings suggest that in human intestinal cells, IFN-λs and IL-22 act independently to clear virus infections. IFN-λs induce ISGs to control virus replication and spread, whereas IL-22 increases cell proliferation to eliminate infected cells and repair the damage epithelium. Although these two cytokines do not act synergistically, each plays a key function in the protection of human IECs.

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来源期刊
CiteScore
3.80
自引率
0.00%
发文量
78
审稿时长
2.2 months
期刊介绍: Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.
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