NCF1, also known as neutrophil cytosolic factor 1 and encoding the p47phox subunit of the phagocyte NADPH oxidase, is essential in reactive oxygen species (ROS) production [3,4,6,7,8]. ROS regulated by NCF1 is involved in multiple pathways, affecting immune and inflammatory responses, and iron homeostasis [1,3]. Genetic models, such as gene knockout mice, have been crucial for studying its function in vivo.

In mouse models, Ncf1 knockout in smooth muscle cells exacerbates angiotensin II-induced aortic aneurysm and dissection by activating the STING pathway, indicating its role in preventing SMC apoptosis [2]. In the context of metabolic dysfunction-associated steatohepatitis (MASH), macrophage NCF1, but not dendritic cell NCF1, triggers Kupffer cell (KC) iron overload, ferroptosis, and monocyte-derived macrophage infiltration, aggravating MASH progression [1]. Also, the Ncf1m1j mutation, causing a deficient ROS response, alleviates antigen-induced pulmonary inflammation, enhancing Th1 response and deactivating group 2 innate lymphoid cells (ILC2) [5].

In conclusion, NCF1 plays a vital role in regulating ROS-related biological processes. Studies using Ncf1 knockout or mutated mouse models have revealed its significance in diseases like aortic aneurysm, MASH, and pulmonary inflammation. These findings provide insights into potential therapeutic targets for treating related diseases by modulating NCF1 function.

References:

1. Zhang, Jing, Wang, Yu, Fan, Meiyang, Lu, Shemin, Holmdahl, Rikard. 2024. Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH. In Cell metabolism, 36, 1745-1763.e6. doi:10.1016/j.cmet.2024.05.008. https://pubmed.ncbi.nlm.nih.gov/38851189/

2. Liu, Hao, Yang, Peiwen, Chen, Shu, Ye, Ping, Xia, Jiahong. . Ncf1 knockout in smooth muscle cells exacerbates angiotensin II-induced aortic aneurysm and dissection by activating the STING pathway. In Cardiovascular research, 120, 1081-1096. doi:10.1093/cvr/cvae081. https://pubmed.ncbi.nlm.nih.gov/38639325/

3. Holmdahl, Rikard, Sareila, Outi, Olsson, Lina M, Bäckdahl, Liselotte, Wing, Kajsa. . Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation. In Immunological reviews, 269, 228-47. doi:10.1111/imr.12378. https://pubmed.ncbi.nlm.nih.gov/26683156/

4. Zhang, Liang, Wax, Jacqueline, Huang, Renliang, Petersen, Frank, Yu, Xinhua. 2022. Meta-Analysis and Systematic Review of the Association between a Hypoactive NCF1 Variant and Various Autoimmune Diseases. In Antioxidants (Basel, Switzerland), 11, . doi:10.3390/antiox11081589. https://pubmed.ncbi.nlm.nih.gov/36009308/

5. Li, Mengyao, Zhang, Wentao, Zhang, Jing, Holmdahl, Rikard, Lu, Shemin. 2021. Ncf1 Governs Immune Niches in the Lung to Mediate Pulmonary Inflammation in Mice. In Frontiers in immunology, 12, 783944. doi:10.3389/fimmu.2021.783944. https://pubmed.ncbi.nlm.nih.gov/34970267/

6. Kuhns, Douglas B, Hsu, Amy P, Sun, David, Wu, Xiaolin, Gallin, John I. . NCF1 (p47phox)-deficient chronic granulomatous disease: comprehensive genetic and flow cytometric analysis. In Blood advances, 3, 136-147. doi:10.1182/bloodadvances.2018023184. https://pubmed.ncbi.nlm.nih.gov/30651282/

7. Luo, Huqiao, Urbonaviciute, Vilma, Saei, Amir Ata, Zubarev, Roman A, Holmdahl, Rikard. 2023. NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions. In JCI insight, 8, . doi:10.1172/jci.insight.164875. https://pubmed.ncbi.nlm.nih.gov/36853827/

8. Meng, Yao, Ma, Jianyang, Yao, Chao, Zhou, Haibo, Shen, Nan. . The NCF1 variant p.R90H aggravates autoimmunity by facilitating the activation of plasmacytoid dendritic cells. In The Journal of clinical investigation, 132, . doi:10.1172/JCI153619. https://pubmed.ncbi.nlm.nih.gov/35788118/