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白细胞介素-27诱导干扰素/信号转导和转录激活因子1依赖性基因，并增强TIGIT HIV Gag特异性T细胞的功能。

IL-27 induces IFN/STAT1-dependent genes and enhances function of TIGIT HIVGag-specific T cells.

作者信息

Cheng Jie, Myers Timothy G, Levinger Callie, Kumar Princy, Kumar Jai, Goshu Bruktawit A, Bosque Alberto, Catalfamo Marta

机构信息

Department of Microbiology and Immunology, Georgetown University School of Medicine, 3970 Reservoir Road, N.W, New Research Building, Room EG19A, Washington, DC 20057, USA.

Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

iScience. 2021 Dec 9;25(1):103588. doi: 10.1016/j.isci.2021.103588. eCollection 2022 Jan 21.

DOI:10.1016/j.isci.2021.103588
PMID:35005538
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8717455/
Abstract

HIV-specific T cells have diminished effector function and fail to control/eliminate the virus. IL-27, a member of the IL-6/IL-12 cytokine superfamily has been shown to inhibit HIV replication. However, whether or not IL-27 can enhance HIV-specific T cell function is largely unknown. In the present manuscript, we investigated the role of IL-27 signaling in human T cells by evaluating the global transcriptional changes related to the function of HIV-specific T cells. We found that T cells from people living with HIV (PLWH), expressed higher levels of STAT1 leading to enhanced STAT1 activation upon IL-27 stimulation. Observed IL-27 induced transcriptional changes were associated with IFN/STAT1-dependent pathways in CD4 and CD8 T cells. Importantly, IL-27 dependent modulation of T-bet expression promoted IFNγ secretion by TIGITHIV-specific T cells. This new immunomodulatory effect of IL-27 on HIV-specific T cell function suggests its potential therapeutic use in cure strategies.

摘要

HIV特异性T细胞的效应功能减弱，无法控制/清除病毒。白细胞介素-27（IL-27）是IL-6/IL-12细胞因子超家族的成员，已被证明可抑制HIV复制。然而，IL-27是否能增强HIV特异性T细胞功能在很大程度上尚不清楚。在本论文中，我们通过评估与HIV特异性T细胞功能相关的整体转录变化，研究了IL-27信号在人T细胞中的作用。我们发现，HIV感染者（PLWH）的T细胞表达更高水平的信号转导和转录激活因子1（STAT1），导致在IL-27刺激下STAT1激活增强。观察到的IL-27诱导的转录变化与CD4和CD8 T细胞中干扰素/STAT1依赖性途径相关。重要的是，IL-27对T-bet表达的依赖性调节促进了TIGITHIV特异性T细胞分泌干扰素γ。IL-27对HIV特异性T细胞功能的这种新的免疫调节作用表明其在治愈策略中的潜在治疗用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/14c6eeb91807/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/42e85130eb7d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/3993692640a1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/1165cf7ae1a2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/1599b307cdfd/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/4477b32957d1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/14c6eeb91807/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/42e85130eb7d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/3993692640a1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/1165cf7ae1a2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/1599b307cdfd/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/4477b32957d1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1521/8717455/14c6eeb91807/gr5.jpg

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本文引用的文献

[1]
An ultrasensitive planar array p24 Gag ELISA to detect HIV-1 in diverse biological matrixes.

Sci Rep. 2021-12-8

[2]
Transcriptomic Profiling of Human Effector and Regulatory T Cell Subsets Identifies Predictive Population Signatures.

Immunohorizons. 2020-10-9

[3]
Early precursor T cells establish and propagate T cell exhaustion in chronic infection.

Nat Immunol. 2020-10

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The Role of Immunomodulatory Receptors in the Pathogenesis of HIV Infection: A Therapeutic Opportunity for HIV Cure?

Front Immunol. 2020

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Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer.

Genome Med. 2020-2-28

[6]
IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors.

Immunohorizons. 2019-1-15

[7]
Altered differentiation is central to HIV-specific CD4 T cell dysfunction in progressive disease.

Nat Immunol. 2019-7-15

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IL-27 posttranslationally regulates Y-box binding protein-1 to inhibit HIV-1 replication in human CD4+ T cells.

AIDS. 2019-10-1

[9]
IL-27 promotes the expansion of self-renewing CD8 T cells in persistent viral infection.

J Exp Med. 2019-6-4

[10]
A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine.

Proc Natl Acad Sci U S A. 2019-1-16

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