Irf7, an interferon regulatory factor, is a master transcriptional factor pivotal for producing IFN-I and regulating the innate immune response. It is involved in multiple signaling pathways, such as those triggered by pathogen-recognition receptors (PRRs) in response to pathogenic nucleic acids. It also plays a role in processes like transcription, translation, and post-translational modifications. Its dimerization and nuclear translocation are crucial steps in its function. Aberrant production of type I IFNs associated with Irf7 dysregulation is linked to diseases like cancers and autoimmune disorders [1,4].

In sepsis-induced acute lung injury, Irf7 transcriptionally activates Srg3, which promotes ferroptosis and M1 macrophage polarization via the NF-κB signaling pathway, exacerbating the symptoms [2]. In Candida albicans infection, Irf7 exacerbates the infection by compromising macrophage phagocytosis and killing capacity through regulating CD209 expression and autophagy-mediated killing, independent of its IFN-producing function [3]. In osteosarcoma, Irf7 acts as a tumor suppressor, inhibiting the Warburg effect by transcriptionally suppressing PKM2 [5]. In a case of an infant with recurrent herpes simplex virus infection, rare missense variants in Irf7, along with UNC93B1, were associated with blunted type I IFN response and higher intracellular viral titers upon HSV-1 challenge [6].

In summary, Irf7 is essential for innate immune regulation, especially in IFN-I production. Studies using gene-knockout models, directly or indirectly, have revealed its role in various disease conditions including sepsis-induced lung injury, fungal infections, osteosarcoma, and viral infections. These findings contribute to our understanding of disease mechanisms and may provide potential therapeutic targets for these diseases.

References:

1. Ma, Wei, Huang, Gang, Wang, Zhi, Wang, Li, Gao, Qiangguo. 2023. IRF7: role and regulation in immunity and autoimmunity. In Frontiers in immunology, 14, 1236923. doi:10.3389/fimmu.2023.1236923. https://pubmed.ncbi.nlm.nih.gov/37638030/

2. Ling, Xinyu, Wei, Shiyou, Ling, Dandan, Wang, Qiuyun, Yuan, Zhize. 2023. Irf7 regulates the expression of Srg3 and ferroptosis axis aggravated sepsis-induced acute lung injury. In Cellular & molecular biology letters, 28, 91. doi:10.1186/s11658-023-00495-0. https://pubmed.ncbi.nlm.nih.gov/37946128/

3. Qing, Furong, Sui, Lina, He, Wenji, Guo, Tianfu, Liu, Zhiping. . IRF7 Exacerbates Candida albicans Infection by Compromising CD209-Mediated Phagocytosis and Autophagy-Mediated Killing in Macrophages. In Journal of immunology (Baltimore, Md. : 1950), 212, 1932-1944. doi:10.4049/jimmunol.2300826. https://pubmed.ncbi.nlm.nih.gov/38709167/

4. Ning, S, Pagano, J S, Barber, G N. 2011. IRF7: activation, regulation, modification and function. In Genes and immunity, 12, 399-414. doi:10.1038/gene.2011.21. https://pubmed.ncbi.nlm.nih.gov/21490621/

5. Li, Zhikun, Geng, Mei, Ye, Xiaojian, Zhang, Xiangyang, Xu, Wei. 2022. IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma. In International journal of biological sciences, 18, 30-42. doi:10.7150/ijbs.65255. https://pubmed.ncbi.nlm.nih.gov/34975316/

6. Tucker, Megan H, Yu, Wei, Menden, Heather, Raje, Nikita, Sampath, Venkatesh. 2023. IRF7 and UNC93B1 variants in an infant with recurrent herpes simplex virus infection. In The Journal of clinical investigation, 133, . doi:10.1172/JCI154016. https://pubmed.ncbi.nlm.nih.gov/37097753/