Irf1-KO Mouse

Irf1, the eponymous member of the interferon regulatory factor (IRF) family, was initially recognized as a nuclear factor that binds and activates type I interferon gene promoters. It is involved in diverse biological functions, playing a key role in the body's defense against invading pathogens, including viruses [4]. It also participates in regulating various cellular processes such as cell death, inflammation, and immune cell activation, contributing to its overall biological importance in maintaining health. Genetic models, like gene knockout (KO) mouse models, have been valuable for studying its functions.

In tumor-related research, loss-of-function experiments show that disrupting the phase separation of KAT8-Irf1 can diminish PD-L1 expression and promote antitumor immunity, suggesting Irf1's role in tumor immune escape regulation [1]. In endometrial cancer, wild-type SPOP binds to Irf1 and triggers its degradation to suppress PD-L1 up-regulation, while SPOP mutants stabilize Irf1 and upregulate PD-L1, accelerating xenograft tumor growth [3]. In osteoarthritis (OA), the knockdown of Irf1 in OA-induced rats mitigated OA-like symptoms, including inflammatory infiltration and cartilage degradation [2,7]. In septic acute respiratory distress syndrome, knockout of Irf1 alleviated lung injury and M1-polarized infiltration [6]. In hematopoietic stem cells (HSCs), loss of Irf1 from mouse HSCs impairs self-renewal and increases stress-induced proliferation [5].

In conclusion, Irf1 is a crucial regulator in multiple biological processes. Through model-based research, especially KO/CKO mouse models, its functions in tumor immune escape, osteoarthritis, sepsis-related lung injury, and HSC maintenance have been revealed. These findings contribute to understanding the mechanisms of related diseases and may offer potential therapeutic targets.

References:

1. Wu, Yuanzhong, Zhou, Liwen, Zou, Yezi, Zheng, Limin, Kang, Tiebang. 2023. Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity. In Nature cancer, 4, 382-400. doi:10.1038/s43018-023-00522-1. https://pubmed.ncbi.nlm.nih.gov/36894639/

2. Tang, Hao, Gong, Xiaoshan, Dai, Jingjin, Deng, Jiezhong, Dong, Shiwu. 2023. The IRF1/GBP5 axis promotes osteoarthritis progression by activating chondrocyte pyroptosis. In Journal of orthopaedic translation, 44, 47-59. doi:10.1016/j.jot.2023.11.005. https://pubmed.ncbi.nlm.nih.gov/38229660/

3. Gao, Kun, Shi, Qing, Gu, Ye, Wang, Chenji, Wan, Xiaoping. 2022. SPOP mutations promote tumor immune escape in endometrial cancer via the IRF1-PD-L1 axis. In Cell death and differentiation, 30, 475-487. doi:10.1038/s41418-022-01097-7. https://pubmed.ncbi.nlm.nih.gov/36481790/

4. Feng, Hui, Zhang, Yi-Bing, Gui, Jian-Fang, Lemon, Stanley M, Yamane, Daisuke. 2021. Interferon regulatory factor 1 (IRF1) and anti-pathogen innate immune responses. In PLoS pathogens, 17, e1009220. doi:10.1371/journal.ppat.1009220. https://pubmed.ncbi.nlm.nih.gov/33476326/

5. Rundberg Nilsson, Alexandra J S, Xian, Hongxu, Shalapour, Shabnam, Cammenga, Jörg, Karin, Michael. 2023. IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance. In Science advances, 9, eadg5391. doi:10.1126/sciadv.adg5391. https://pubmed.ncbi.nlm.nih.gov/37889967/

6. Wang, Ailing, Kang, Xueli, Wang, Jing, Zhang, Shi. 2022. IFIH1/IRF1/STAT1 promotes sepsis associated inflammatory lung injury via activating macrophage M1 polarization. In International immunopharmacology, 114, 109478. doi:10.1016/j.intimp.2022.109478. https://pubmed.ncbi.nlm.nih.gov/36462334/

7. Wang, Dong, Zhang, Yujun, Zhang, Liangping, Zhu, Hang, Pan, Hao. 2024. IRF1 governs the expression of SMARCC1 via the GCN5-SETD2 axis and actively engages in the advancement of osteoarthritis. In Journal of orthopaedic translation, 45, 211-225. doi:10.1016/j.jot.2024.01.002. https://pubmed.ncbi.nlm.nih.gov/38586591/