Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Department of Geriatrics, Institute of Gerontology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Mol Immunol. 2024 Nov;175:146-154. doi: 10.1016/j.molimm.2024.10.002. Epub 2024 Oct 21.
Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses DNA in a sequence-independent manner, triggering cGAMP synthesis, which activates stimulator of interferon genes (STING) and the subsequent expression of type I interferons, tumour necrosis factor alpha (TNF-α) and other proinflammatory factors in two downstream pathways. However, the function of the cGASSTING pathway in γδ T cells remains unclear. The γδ T-cell population differs from the innate-like lymphocyte population, particularly with respect to tissue distribution, indicating the unique potential of γδ T cells in treating infections and cancers. On the basis of accumulating evidence, cGAS activity is modulated by protein posttranslational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation, which affect multiple cGAS functions. Thus, here, we summarize recent research on PTMs of the cGAS protein that modulate γδ T-cell function. An understanding of cGAS features and modulation mechanisms may facilitate the design of therapies for γδ T-cell-related immune diseases and cancer.
环鸟苷酸-腺苷酸 (cGAMP) 合酶 (cGAS) 以非序列依赖的方式感知 DNA，触发 cGAMP 的合成，这激活干扰素基因刺激物 (STING)，并随后在两条下游途径中表达 I 型干扰素、肿瘤坏死因子-α (TNF-α) 和其他促炎因子。然而，cGAS-STING 途径在 γδ T 细胞中的功能尚不清楚。γδ T 细胞群体不同于先天样淋巴细胞群体，特别是在组织分布方面，这表明 γδ T 细胞在治疗感染和癌症方面具有独特的潜力。基于不断积累的证据，cGAS 活性受到蛋白质翻译后修饰 (PTMs) 的调节，包括磷酸化、O-GlcNAc 化、乙酰化、泛素化和甲基化，这些修饰影响 cGAS 的多种功能。因此，在这里，我们总结了最近关于调节 γδ T 细胞功能的 cGAS 蛋白 PTM 的研究。对 cGAS 特征和调节机制的理解可能有助于设计与 γδ T 细胞相关的免疫疾病和癌症的治疗方法。
