Fcna-KO Mouse

Fcna, also known as Ficolin A, is a recognition molecule that plays a crucial role in the lectin complement pathway in the innate immune system. It complexes with MBL-associated serine proteases and acts as a soluble pattern recognition molecule [2].

In KO mouse models, Fcna knockout alleviated sepsis-induced severe lung injury in mice by restoring gut Akkermansia to inhibit the S100A4/STAT3 pathway. This was evidenced by increased body weight change, decreased wet/dry weight of lung tissue, reduced inflammatory infiltration, and decreased levels of inflammatory cytokines [1]. Additionally, Fcna knockout attenuated lung inflammation and inhibited neutrophil extracellular traps (NETs) formation in the LPS-induced mouse model, suggesting that Fcna may exacerbate severe lung injury through NETs mediated by Gasdermin D-induced pyroptosis [3]. Fcna-deficient mice were also more susceptible to Streptococcus pneumoniae infection, indicating its importance in host defense against this pathogen [2].

In conclusion, Fcna is essential for innate immunity, especially in defense against certain infections. Through gene knockout studies in mice, it has been shown to play a significant role in the pathogenesis of sepsis-induced severe lung injury and LPS-induced lung injury. These findings provide insights into potential therapeutic targets for treating related diseases.

References:

1. Wu, Xu, Xuan, Weixia, Yang, Xiaoping, Cao, Bin, Jiang, Yongliang. 2023. Ficolin A knockout alleviates sepsis-induced severe lung injury in mice by restoring gut Akkermansia to inhibit S100A4/STAT3 pathway. In International immunopharmacology, 121, 110548. doi:10.1016/j.intimp.2023.110548. https://pubmed.ncbi.nlm.nih.gov/37356123/

2. Endo, Yuichi, Takahashi, Minoru, Iwaki, Daisuke, Schwaeble, Wilhelm J, Fujita, Teizo. 2012. Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection. In Journal of immunology (Baltimore, Md. : 1950), 189, 5860-6. doi:10.4049/jimmunol.1200836. https://pubmed.ncbi.nlm.nih.gov/23150716/

3. Huang, Li, Tan, Xiaowu, Xuan, Weixia, Jiang, Yongliang, Wu, Xu. 2024. Ficolin-A/2 Aggravates Severe Lung Injury through Neutrophil Extracellular Traps Mediated by Gasdermin D-Induced Pyroptosis. In The American journal of pathology, 194, 989-1006. doi:10.1016/j.ajpath.2024.02.011. https://pubmed.ncbi.nlm.nih.gov/38442803/