Ccl25, a chemokine, is the exclusive ligand of chemokine receptor 9 (CCR9). Chemokines regulate cell migration, and Ccl25 is involved in inflammation, leukocyte trafficking, and immunoregulation. It also plays a role in multiple signaling pathways such as NF-κB, P38 MAPK, and PI3K/AKT, influencing various biological processes and diseases [1,2,3,6]. Genetic models, like gene knockout mouse models, can be valuable for studying its functions.

Functional gene knockout mouse models have been used to investigate the role of CCR9/ Ccl25 in adriamycin-induced cardiomyopathy. In this case, CCR9 knockout reversed the harmful effects of adriamycin on the heart, including decreased AMPK activity, increased mitochondrial dysfunction, fibrosis, oxidative stress, and apoptosis, suggesting that Ccl25/CCR9 signaling is detrimental in this context [4]. In acute liver failure (ALF) mouse models, anti-Ccl25 treatment suppressed ALF development, as Ccl25 contributes to ALF by inducing macrophage-mediated inflammation via NF-κB signaling activation [5].

In conclusion, Ccl25 is crucial in inflammation and disease-related processes. Gene knockout mouse models have revealed its role in diseases such as adriamycin-induced cardiomyopathy and ALF. Understanding Ccl25's functions through these models provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Xu, Baoping, Deng, Chao, Wu, Xue, Yang, Zhi, Yang, Yang. 2020. CCR9 and CCL25: A review of their roles in tumor promotion. In Journal of cellular physiology, 235, 9121-9132. doi:10.1002/jcp.29782. https://pubmed.ncbi.nlm.nih.gov/32401349/

2. Wu, Xue, Sun, Meng, Yang, Zhi, Liu, Yonglin, Yang, Yang. 2021. The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases. In Frontiers in cell and developmental biology, 9, 686548. doi:10.3389/fcell.2021.686548. https://pubmed.ncbi.nlm.nih.gov/34490243/

3. Xia, Demeng, Wang, Sheng, Liu, Anwei, Zhou, Panyu, Xu, Shuogui. 2022. CCL25 Inhibition Alleviates Sepsis-Induced Acute Lung Injury and Inflammation. In Infection and drug resistance, 15, 3309-3321. doi:10.2147/IDR.S352544. https://pubmed.ncbi.nlm.nih.gov/35782530/

4. Wu, Xue, Wang, Zheng, Liang, Zhenxing, Wei, Jinhong, Yang, Yang. 2024. Pleiotropic role of CCR9/CCL25 signaling in adriamycin-induced cardiomyopathy. In Journal of advanced research, , . doi:10.1016/j.jare.2024.10.018. https://pubmed.ncbi.nlm.nih.gov/39442876/

5. Sun, Fei, Wang, Jingwei, Ji, Xiangfen, Gao, Shuai, Wang, Kai. 2024. CCL25 contributes to the pathogenesis of D-Gal/LPS-induced acute liver failure. In Journal of gastroenterology and hepatology, 39, 2880-2891. doi:10.1111/jgh.16732. https://pubmed.ncbi.nlm.nih.gov/39233339/

6. Chai, Songling, Wen, Zhihao, Zhang, Rongxin, Wang, Fu, Gao, Lu. 2022. CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway. In PeerJ, 10, e13844. doi:10.7717/peerj.13844. https://pubmed.ncbi.nlm.nih.gov/36003306/