Ding Huihui, Wang Gongfu, Yu Zhen, Sun Huimin, Wang Lu
School of Pharmacy, Shandong First Medical University, Jinan, Shandong, China.
Center for Drug Evaluation, China Food and Drug Administration (CFDA), Beijing, China.
Biomed Pharmacother. 2022 Nov;155:113683. doi: 10.1016/j.biopha.2022.113683. Epub 2022 Sep 12.
IFN-γ, a soluble cytokine being produced by T lymphocytes, macrophages, mucosal epithelial cells, or natural killer cells, is able to bind to the IFN-γ receptor (IFNγR) and in turn activate the Janus kinase (JAK)-signal transducer and transcription protein (STAT) pathway and induce expression of IFN-γ-stimulated genes. IFN-γ is critical for innate and adaptive immunity and aberrant IFN-γ expression and functions have been associated with different human diseases. However, the IFN-γ/IFNγR signaling could be a double-edged sword in cancer development because the tissue microenvironments could determine its anti- or pro-tumorigenic activities. The IFNγR protein consists of two IFNγR1 and IFNγR2 chains, subunits of which play different roles under certain conditions. This review assessed IFNγR polymorphisms, expression and functions in development and progression of various human diseases in an IFN-γ-dependent or independent manner. This review also discussed tumor microenvironment, microbial infection, and vital molecules in the IFN-γ upstream signaling that might regulate IFNγR expression, drug resistance, and druggable strategy, to provide evidence for further application of IFNγR.
干扰素-γ是一种由T淋巴细胞、巨噬细胞、黏膜上皮细胞或自然杀伤细胞产生的可溶性细胞因子，它能够与干扰素-γ受体（IFNγR）结合，进而激活Janus激酶（JAK）-信号转导子和转录蛋白（STAT）通路，并诱导干扰素-γ刺激基因的表达。干扰素-γ对先天性和适应性免疫至关重要，其异常表达和功能与多种人类疾病相关。然而，在癌症发展过程中，干扰素-γ/IFNγR信号可能是一把双刃剑，因为组织微环境可以决定其抗肿瘤或促肿瘤活性。IFNγR蛋白由两条IFNγR1和IFNγR2链组成，在某些情况下，其亚基发挥不同作用。本综述以依赖或不依赖干扰素-γ的方式评估了IFNγR多态性、在各种人类疾病发生发展中的表达及功能。本综述还讨论了肿瘤微环境、微生物感染以及干扰素-γ上游信号中可能调节IFNγR表达、耐药性和可靶向策略的重要分子，为IFNγR的进一步应用提供依据。
