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锰通过cGAS-STING介导的UTX表达增强自然杀伤细胞功能。

Manganese boosts natural killer cell function via cGAS-STING mediated UTX expression.

作者信息

Ming Qianyi, Liu Jiejie, Lv Zijian, Wang Tiance, Fan Runjia, Zhang Yan, Chen Meixia, Sun Yingli, Han Weidong, Mei Qian

机构信息

Department of Bio-Therapeutic the First Medical Center Chinese PLA General Hospital Beijing China.

Central Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital Chinese Academic of Medical Sciences and Peking Union Medical College Shenzhen China.

出版信息

MedComm (2020). 2024 Aug 28;5(9):e683. doi: 10.1002/mco2.683. eCollection 2024 Sep.

DOI:10.1002/mco2.683
PMID:39206412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11351689/
Abstract

Natural killer (NK) cells play a crucial role in both innate immunity and the activation of adaptive immunity. The activating effect of Mn on cyclic GMP-AMP(cGAS)-stimulator of interferon genes (STING signaling has been well known, but its effect on NK cells remains elusive. In this study, we identified the vital role of manganese (Mn) in NK cell activation. Mn directly boosts cytotoxicity of NK cells and promotes the cytokine secretion by NK cells, thereby activating CD8+ T cells and enhancing their antitumor activity. Furthermore, Mn can simultaneously activate NK-cell intrinsic cGAS and STING and consequently augment the expression of ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX to promote the responsiveness of NK cells. Our results contribute to a broader comprehension of how cGAS-STING regulates NK cells. As a potent agonist of cGAS-STING, Mn provides a promising option for NK cell-based immunotherapy of cancers.

摘要

自然杀伤（NK）细胞在固有免疫和适应性免疫激活中均发挥着关键作用。锰（Mn）对环磷酸鸟苷-腺苷酸合成酶（cGAS）-干扰素基因刺激因子（STING）信号通路的激活作用已为人熟知，但其对NK细胞的影响仍不清楚。在本研究中，我们确定了锰（Mn）在NK细胞激活中的重要作用。Mn直接增强NK细胞的细胞毒性并促进NK细胞分泌细胞因子，从而激活CD8+ T细胞并增强其抗肿瘤活性。此外，Mn可同时激活NK细胞内在的cGAS和STING，并因此增加X染色体上普遍转录的四肽重复序列（UTX）的表达，以促进NK细胞的反应性。我们的结果有助于更全面地理解cGAS-STING如何调节NK细胞。作为cGAS-STING的有效激动剂，Mn为基于NK细胞的癌症免疫治疗提供了一个有前景的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/6629dece2794/MCO2-5-e683-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/43cd3326cc54/MCO2-5-e683-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/68660780cc32/MCO2-5-e683-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/004a2fd78513/MCO2-5-e683-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/77f6a8b21ca8/MCO2-5-e683-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/92f67cb78a76/MCO2-5-e683-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/6629dece2794/MCO2-5-e683-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/43cd3326cc54/MCO2-5-e683-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/68660780cc32/MCO2-5-e683-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/004a2fd78513/MCO2-5-e683-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/77f6a8b21ca8/MCO2-5-e683-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/92f67cb78a76/MCO2-5-e683-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5897/11351689/6629dece2794/MCO2-5-e683-g001.jpg

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Interferon-γ couples CD8 T cell avidity and differentiation during infection.干扰素-γ 在感染过程中连接 CD8 T 细胞的亲和力和分化。
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The cancer-immunity cycle: Indication, genotype, and immunotype.癌症免疫周期：指征、基因型和免疫型。
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