Ccl25, a chemokine, is the exclusive ligand of chemokine receptor 9 (CCR9). Chemokines are small chemotactic cytokines regulating cell migration, and Ccl25 is involved in leukocyte trafficking, immunoregulation, and inflammation [1,2,3]. It can interact with CCR9 to activate related signaling pathways, such as the P38 MAPK and NF-κB pathways, influencing various biological processes [3,5]. Ccl25 has significant importance in the development of multiple diseases, including cancer, inflammation-associated diseases, and acute lung injury [1,2,3]. Genetic models, like gene knockout mouse models, can be used to study its functions.

In a male C57BL/6 mice cecal ligation puncture (CLP) model of sepsis, inhibition of Ccl25 significantly reduced inflammatory cytokine expression, alleviating lung tissue damage, suggesting Ccl25 contributes to the development of acute lung injury by modulating microvascular endothelial cell functions [3]. In D-Gal/LPS-induced acute liver failure mouse models, Ccl25 contributed to the pathogenesis by inducing macrophage-mediated inflammation via activation of the NF-κB signaling, and anti-Ccl25 treatment suppressed acute liver failure [5]. In adriamycin-induced cardiomyopathy mouse models, CCR9 and Ccl25 levels increased, and CCR9 overexpression aggravated cardiac dysfunction, while CCR9 knockdown reversed the harmful effects of adriamycin, indicating the role of the CCR9/Ccl25 axis in this condition [4].

In conclusion, Ccl25 is crucial in inflammation, immunoregulation, and disease development. Gene knockout or knockdown mouse models have revealed its roles in acute lung injury, acute liver failure, and adriamycin-induced cardiomyopathy. Understanding Ccl25 functions through these models provides insights into disease mechanisms and potential therapeutic targets for related diseases.