Nfil3, also known as E4 binding protein 4 (E4BP4), is a proline-and acidic-residue-rich (PAR) bZIP transcription factor. It is essential in regulating circadian rhythms and cell viability. NFIL3 is involved in multiple pathways, such as lipid metabolism, inflammatory response, and immune cell regulation, and thus holds great biological importance. Genetic models, especially knockout (KO) mouse models, have been crucial in studying its functions [1].

In a KO mouse model for EAE, NFIL3 deficiency alleviated the disease through regulating different immune cell subsets. At the peak of EAE, Th17 cells decreased within the CNS, accompanied by lower clinical scores and milder neuroinflammation and demyelination in NFIL3 knockout EAE mice. Outside the CNS, PD-1 and ICOS on CD4+T cells increased, whereas Th2, Th9, CD8+CD103+T cells and GM-CSF+CD4+T cells decreased. Also, the pro-inflammatory capacity of NFIL3 -/- CD11c+ dendritic cells was impaired while the anti-inflammatory capacity was promoted [2]. In another preclinical model, Nfil3-deficient mice upregulated IL-1β production, with more severe arthritis symptoms on disease induction, indicating that NFIL3 mutation can sensitize for arthritis development in mice [3].

In conclusion, NFIL3 is a key regulator in circadian rhythms, cell viability, lipid metabolism, inflammatory response, and immune cell regulation. Model-based research, especially using KO mouse models, has revealed its role in diseases like EAE and arthritis. These findings provide insights into the molecular mechanisms underlying these diseases and potential therapeutic targets related to NFIL3.

References:

1. Zeng, Guang-Gui, Zhou, Jing, Jiang, Wan-Li, Zhang, Shi-Qian, Tang, Chao-Ke. 2023. A Potential Role of NFIL3 in Atherosclerosis. In Current problems in cardiology, 49, 102096. doi:10.1016/j.cpcardiol.2023.102096. https://pubmed.ncbi.nlm.nih.gov/37741601/

2. Chen, Zhigang, Fan, Rong, Liang, Jie, Zheng, Song Guo, Jiang, Ying. 2021. NFIL3 deficiency alleviates EAE through regulating different immune cell subsets. In Journal of advanced research, 39, 225-235. doi:10.1016/j.jare.2021.10.011. https://pubmed.ncbi.nlm.nih.gov/35777910/

3. Schlenner, Susan, Pasciuto, Emanuela, Lagou, Vasiliki, Wouters, Carine, Liston, Adrian. 2018. NFIL3 mutations alter immune homeostasis and sensitise for arthritis pathology. In Annals of the rheumatic diseases, 78, 342-349. doi:10.1136/annrheumdis-2018-213764. https://pubmed.ncbi.nlm.nih.gov/30552177/