LRRC25, leucine-rich repeat-containing protein 25, is involved in multiple biological processes and signaling pathways. It is a negative regulator in the NF-κB signaling pathway, the RLR-mediated type I interferon (IFN) signaling pathway, and can also affect autophagy-related processes. These functions are crucial for maintaining immune homeostasis, cell differentiation, and normal physiological states [2,3]. Genetic models, especially KO mouse models, are valuable for studying its functions.

In a mouse model of Mycobacterium tuberculosis infection, silencing LRRC25 in BV2 cells led to a decrease in the proportion of infected cells, and an increase in IFN-γ and ISG15 levels, indicating that LRRC25 negatively regulates anti-tuberculosis immunity in microglia by degrading free ISG15 and inhibiting IFN-γ secretion [1]. In a study on cardiac hypertrophy, LRRC25 knockout in mice exacerbated cardiac hypertrophy, fibrosis, and inflammation in response to pressure overloading or angiotensin II stimulation, suggesting that down-regulation of LRRC25 contributes to cardiac hypertrophy in a TGF-β1-and NF-κB-dependent manner [4].

In conclusion, LRRC25 plays essential roles in immune regulation, cell differentiation, and preventing pathological cardiac hypertrophy. The use of KO mouse models has significantly enhanced our understanding of its functions in anti-tuberculosis immunity and cardiac hypertrophy, providing potential targets for treating related diseases.

References:

1. Sheng, Gang, Chu, Hongqian, Duan, Huijuan, Sun, Hong, Sun, Zhaogang. 2023. LRRC25 Inhibits IFN-γ Secretion by Microglia to Negatively Regulate Anti-Tuberculosis Immunity in Mice. In Microorganisms, 11, . doi:10.3390/microorganisms11102500. https://pubmed.ncbi.nlm.nih.gov/37894158/

2. Du, Yang, Duan, Tianhao, Feng, Yanchun, Cui, Jun, Wang, Rong-Fu. 2017. LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation. In The EMBO journal, 37, 351-366. doi:10.15252/embj.201796781. https://pubmed.ncbi.nlm.nih.gov/29288164/

3. Feng, Yanchun, Duan, Tianhao, Du, Yang, Cui, Jun, Wang, Rong-Fu. 2017. LRRC25 Functions as an Inhibitor of NF-κB Signaling Pathway by Promoting p65/RelA for Autophagic Degradation. In Scientific reports, 7, 13448. doi:10.1038/s41598-017-12573-3. https://pubmed.ncbi.nlm.nih.gov/29044191/

4. Zhang, Xia, Zhang, Ming-Chao, Wang, Chun-Tian. 2018. Loss of LRRC25 accelerates pathological cardiac hypertrophy through promoting fibrosis and inflammation regulated by TGF-β1. In Biochemical and biophysical research communications, 506, 137-144. doi:10.1016/j.bbrc.2018.09.065. https://pubmed.ncbi.nlm.nih.gov/30340835/