Ccr9, a G protein-coupled chemokine receptor, is expressed on several immune cells like dendritic cells, CD4+ T cells, and B cells [2]. It drives immune cell migration towards gradients of its ligand CCL25, which is mainly produced by gut and thymic epithelial cells. Ccr9 is involved in regulating the occurrence and development of various diseases, and its activation by CCL25 can interact with many signaling pathways, especially those related to tumor chemoresistance, metastasis, and immune-related responses [1,3]. Gene knockout mouse models have been crucial in exploring its physiological functions.

Early research on Ccr9-deficient mouse models confirmed its functions in inflammatory responses [1]. In the context of disease, Ccr9 antagonists have shown potential in retarding the progression of inflammatory bowel disease (IBD) as Ccr9 is a key molecule in leukocyte homing to gut mucosa [4]. In adriamycin-induced cardiomyopathy, Ccr9 overexpression aggravated cardiac dysfunction, while Ccr9 knockdown reversed the harmful effects of adriamycin, indicating its role in cardiac-related pathologies [5]. In T-cell acute lymphoblastic leukemia (T-ALL), overexpression of Ccr9 promoted disease progression by enhancing cholesterol biosynthesis [6].

In summary, Ccr9 plays essential roles in inflammation, immunity, and various disease conditions. Model-based research, especially Ccr9-deficient mouse models, has significantly contributed to understanding its functions in IBD, cardiomyopathy, and T-ALL, providing insights into potential therapeutic targets for these diseases.